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Catch-up growth, a risk factor for type 2 diabetes, is characterized by hyperinsulinemia and accelerated body fat recovery. Using a rat model of semistarvation-refeeding that exhibits catch-up fat, we previously reported that during refeeding on a low-fat diet, glucose tolerance is normal but insulin-dependent glucose utilization is decreased in skeletal muscle and increased in adipose tissue, where de novo lipogenic capacity is concomitantly enhanced. Here we report that isocaloric refeeding on a high-fat (HF) diet blunts the enhanced in vivo insulin-dependent glucose utilization for de novo lipogenesis (DNL) in adipose tissue. These are shown to be early events of catch-up growth that are independent of hyperphagia and precede the development of overt adipocyte hypertrophy, adipose tissue inflammation, or defective insulin signaling. These results suggest a role for enhanced DNL as a glucose sink in regulating glycemia during catch-up growth, which is blunted by exposure to an HF diet, thereby contributing, together with skeletal muscle insulin resistance, to the development of glucose intolerance. Our findings are presented as an extension of the Randle cycle hypothesis, whereby the suppression of DNL constitutes a mechanism by which dietary lipids antagonize glucose utilization for storage as triglycerides in adipose tissue, thereby impairing glucose homeostasis during catch-up growth. [ABSTRACT FROM AUTHOR]

Objective: Catch-up growth, a risk factor for later type 2 diabetes, is characterized by hyperinsulinemia, accelerated body-fat recovery (catch-up fat), and enhanced glucose utilization in adipose tissue. Our objective was to characterize the determinants of enhanced glucose utilization in adipose tissue during catch-up fat.Research Design and Methods: White adipose tissue morphometry, lipogenic capacity, fatty acid composition, insulin signaling, in vivo glucose homeostasis, and insulinemic response to glucose were assessed in a rat model of semistarvation-refeeding. This model is characterized by glucose redistribution from skeletal muscle to adipose tissue during catch-up fat that results solely from suppressed thermogenesis (i.e., without hyperphagia).Results: Adipose tissue recovery during the dynamic phase of catch-up fat is accompanied by increased adipocyte number with smaller diameter, increased expression of genes for adipogenesis and de novo lipogenesis, increased fatty acid synthase activity, increased proportion of saturated fatty acids in triglyceride (storage) fraction but not in phospholipid (membrane) fraction, and no impairment in insulin signaling. Furthermore, it is shown that hyperinsulinemia and enhanced adipose tissue de novo lipogenesis occur concomitantly and are very early events in catch-up fat.Conclusions: These findings suggest that increased adipose tissue insulin stimulation and consequential increase in intracellular glucose flux play an important role in initiating catch-up fat. Once activated, the machinery for lipogenesis and adipogenesis contribute to sustain an increased insulin-stimulated glucose flux toward fat storage. Such adipose tissue plasticity could play an active role in the thrifty metabolism that underlies glucose redistribution from skeletal muscle to adipose tissue. [ABSTRACT FROM AUTHOR]

Background/aims: Coronary heart disease morbidity and mortality are higher in people of South Asian origin than in those of African origin. We investigated whether as young adults without diabetes, people in Mauritius of South Asian descent (Indians) would show a more adverse cardiovascular risk profile that those of predominantly African descent (Creoles), and whether this could be explained by ethnic differences in visceral adiposity or other fat distribution patterns., Methods: The study was conducted in 189 young non-physically active adults, with the following measurements conducted after an overnight fast: anthropometry (weight, height, waist circumference), whole-body and regional body composition by dual-energy x-ray absorptiometry, blood pressure, and blood assays for glycemic (glucose and HbA1c) and lipid profile (triglycerides and cholesterols)., Results: The results indicate higher serum triglycerides and lower HDL cholesterol in men than in women, and in Indians than in Creoles (p < 0.001). No significant differences due to sex or ethnicity are observed in body mass index and waist circumference, but indices of visceral adiposity (visceral/android, visceral/subcutaneous) and visceral-to-peripheral adiposity ratio (visceral/gynoid, visceral/limb) were significantly higher in men than in women, and in Indians than in Creoles. The significant effects of sex and ethnicity on blood lipid profile were either completely abolished or reduced to a greater extent after adjusting for the ratio of visceral-to-peripheral adiposity than for visceral adiposity per se., Conclusions: In young adults in Mauritius, Indians show a more adverse pattern of body fat distribution and blood lipid risk profile than Creoles. Differences in their fat distribution patterns, however, only partially explain their differential atherogenic lipid risk profile, amid a greater impact of visceral-to-peripheral adiposity ratio than that of visceral adiposity per se on sex and ethnic differences in cardiovascular risks; the former possibly reflecting the ratio of hazardous (visceral) adiposity and protective (peripheral) superficial subcutaneous adiposity., (© 2024. The Author(s).)

Purpose: Sales for sugar-sweetened and caffeinated beverages are still rising globally and their consumption has been linked to the development of cardiovascular diseases. However, direct evidence from human interventional studies in response to such beverages is still scarce., Methods: Seven young, non-obese men participated in a randomized crossover study where four test drinks [60 g sucrose + 50 mg caffeine, 60 g sucrose + caffeine-placebo, 50 mg caffeine, and caffeine-placebo] were investigated. Each drink was brought to a total volume of 500 mL with water. Continuous and beat-to-beat hemodynamic monitoring was conducted for 30 min baseline and continued for 90 min after the ingestion of each drink. Measurements included blood pressure, heart rate, stroke volume, cardiac output, total peripheral resistance, index of contractility, and double product., Results: Two-factor ANOVA analysis revealed significant treatment-by-time effects for diastolic blood pressure, heart rate, stroke volume, cardiac output, total peripheral resistance, index of contractility, and double product (all p < 0.01). Diastolic blood pressure and total peripheral resistance increased significantly to caffeine-only (all p < 0.05), while sucrose + caffeine-placebo and sucrose + caffeine both decreased resistance responses (all p < 0.05). Cardiac output increased significantly to sucrose + caffeine-placebo and sucrose + caffeine (all p < 0.05), and on trend for heart rate, stroke volume, and index of contractility (all p between 0.05 and 0.09)., Conclusion: In young, non-obese men, a caffeinated and sucrose-sweetened beverage at concentrations similar to classical commercial Cola products exhibited distinct hemodynamic actions where the presence of sucrose dampened caffeine-induced blood pressure elevations, but at the expense of a tendency to increase cardiac work., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ravussin, Montani and Grasser.)

Societal erosion of daily life low-level physical activity has had a great influence on the obesity epidemic. Given that low fat oxidation is also a risk factor for obesity, we investigated, in a repeated measures design, the dynamics of fat oxidation from a resting state to a light-intensity leg cycling exercise (0-50 watts) in inactive, healthy young adults. Using indirect calorimetry, energy expenditure and the respiratory quotient (RQ) were assessed in a sitting posture at rest and during a cycling exercise in 35 subjects (20 women). The rate of perceived exhaustion (RPE) was assessed using the Borg Scale. During graded leg cycling, the mean RPE did not exceed values corresponding to the exercise being perceived as 'light'. However, analysis of individual data at 50 watts revealed two distinct subgroups among the subjects: those having RPE values corresponding to the exercise being perceived as 'very light to light' and showing no increase in RQ relative to resting levels, as opposed to an increase in RQ in those who perceived the exercise as being 'somewhat hard to hard' ( p < 0.001). Our study in inactive individuals showing that high fat oxidation was maintained during 'light-perceived' physical activity reinforced the potential importance of light physical activity in the prevention of obesity.

Several areas of research into the prevention and treatment of obesity today can be traced to one or more of the scientific works pioneered by Ancel Keys between the 1930s to 1970s in fields that cut across the physiology of extremes and public health nutrition. These range from his classical studies into how body and mind respond to chronic exposure to hypoxia in "The Physiology of Life at High Altitudes" or to simulated famine under controlled laboratory conditions in "The Biology of Human Starvation", the impact of diet and lifestyle on cardiovascular morbidity and mortality in "The Seven Countries Study," to the "Indices of Relative Weight and Obesity" in which he identified what has since been the most widely utilized diagnostic tool to monitor obesity across populations worldwide and which he coined as the body mass index. The contribution of Ancel Keys to medical sciences through his observations, analytical approaches, and research output of his classic studies, and how these have (and continue) to impact on a plethora of current concepts in obesity research today, are embodied in the eight review articles that constitute this supplement reporting the proceedings of the 10th Fribourg Obesity Research Conference. The aim of this introductory paper is to put into perspective the legacy of Ancel Keys to current concepts that are encapsulated in these review articles that cover research areas that include (i) the diagnosis of obesity for health risks; (ii) the role of dietary fat types in the pathogenesis of obesity and cardiometabolic diseases; (iii) the rationale, efficacy and safety of low carbohydrate ketogenic diets, or the therapeutic potential of hypoxic conditioning, in weight management programs; (iv) the psychological and physiological basis of the "famine reaction" that counters therapeutic dieting and facilitates weight regain; and (v) the potential impact of weight cycling and yoyo dieting on risks for later obesity and cardiometabolic diseases., (© 2021 World Obesity Federation.)

The most appropriate type of diets to maintain or lose body weight over the medium to long term has been a matter of controversy and debates for more than half a century. Both voluntarily and coercive food restriction, resulting in negative energy and macronutrient balance and hence weight loss, have not been designed to be maintained for the long term. By contrast, when a classical and traditional type of alimentation is consumed in ad lib conditions (e.g., the Mediterranean "diet"), it generally provides an appropriate nutritional density of essential macronutrients and micronutrients; it is hence appropriate for long-term use, and it provides several benefits for health if the compliance of the individuals is maintained over time. In this short review, we focus on four specific aspects: first, the need to agree on a clear definition of what is "low" versus "high" in terms of total carbohydrate intake and total fat intakes, both generally inversely related, in a representative individual with a certain lifestyle and a certain body morphology; second, the importance of discussing the duration over which it could be prescribed, that is, acute versus chronic conditions, focusing on the comparison between the fashion and often ephemeral low-carbohydrate diet (acute) with the well-recognized traditional Mediterranean type of alimentation (chronic), which includes lifestyle changes; third, the particular metabolic characteristics induced by the low-carbohydrate (high fat) diet, namely, the scramble up of ketone bodies production. The recent debate on ketogenic diets concern whether or not, in iso-energetic conditions, low-carbohydrate diets would significantly enhance energy expenditure. This is an issue that is more "academic" than practical, on the ground that the putative difference of 100-150 kcal/day or so (in the recent studies) is not negligible but within the inherent error of the methodology used to track total energy expenditure in free living conditions by the doubly labeled water technique. Fourth, the potential medical risks and shortcomings of ingesting (over the long term) low-carbohydrate ketogenic diets could exacerbate underlying renal dysfunction, consecutive to the joint combination of high-fat, high-protein diets, particularly in individuals with obesity. This particular diet promotes metabolic acidosis and renal hyperfiltration, which ultimately may contribute to a significant reduction in life expectancy in middle-age people., (© 2021 World Obesity Federation.)

Ancel Keys, whose life spanned over 100 years (1904-2004), made a wealth of seminal scientific and public health contributions. As a physiologist, nutritionist, and public health scientist, he has left his mark on the 20th century by exploring different areas of physiology and nutrition, as well as by contributing to the understanding of basic public health issues. Among his major achievements one can mention in chronological order: studying adaptation to very high altitude, developing the K ration to enable the US military to survive with light but dense food, dissecting the physiology of starvation and nutritional rehabilitation to optimize recovery of functions, uncovering the link between serum cholesterol and heart disease, coordinating the first multi-country epidemiological longitudinal study in nutrition and health, coining the word "body mass index" (BMI), which he showed to be the best body weight index to predict body fat, and promoting the Mediterranean diet for a healthy life style. This review examines the historical events and scientific intrigues that have surrounded Ancel Keys's major classical studies that have ensured him a central place in the history of medical science., (© 2021 World Obesity Federation.)

It is increasingly recognised that the use of BMI cut-off points for diagnosing obesity (OB) and proxy measures for body fatness in a given population needs to take into account the potential impact of ethnicity on the BMI-fat % relationship in order to avoid adiposity status misclassification. This relationship was studied here in 377 Mauritian schoolchildren (200 boys and 177 girls, aged 7-13 years) belonging to the two main ethnic groups: Indian (South Asian descent) and Creole (African/Malagasy descent), with body composition assessed using an isotopic 2H dilution technique as reference. The results indicate that for the same BMI, Indians have more body fat (and less lean mass) than Creoles among both boys and girls: linear regression analysis revealed significantly higher body fat % by 4-5 units (P < 0·001) in Indians than in Creoles across a wide range of BMI (11·6-34·2 kg/m2) and body fat % (5-52 %). By applying Deurenberg's Caucasian-based equation to predict body fat % from WHO-defined BMI thresholds for overweight (OW) and OB, and by recalculating the equivalent BMI values using a Mauritian-specific equation, it is shown that the WHO BMI cut-offs for OB and OW would need to be lowered by 4·6-5·9 units in Indian and 2·0-3·7 units in Creole children in the 7-13-year-old age group. These results have major implications for ethnic-based population research towards improving the early diagnosis of excess adiposity in this multi-ethnic population known to be at high risk for later development of type 2 diabetes and CVD.

The notion that dieting makes some people fatter has in the past decade gained considerable interest from both epidemiological predictions and biological plausibility. Several large-scale prospective studies have suggested that dieting to lose weight is associated with future weight gain and obesity, with such predictions being stronger and more consistent among dieters who are in the normal range of body weight rather than in those with obesity. Furthermore, the biological plausibility that dieting predisposes people who are lean (rather than those with overweight or obesity) to regain more body fat than what had been lost (referred to as fat overshooting) has recently gained support from a re-analysis of data on body composition during weight loss and subsequent weight recovery from the classic longitudinal Minnesota Starvation Experiment. These have revealed an inverse exponential relationship between the amount of fat overshot and initial adiposity, and have suggested that a temporal desynchronization in the recoveries of fat and lean tissues, in turn residing in differences in lean-fat partitioning during weight loss vs. during weight recovery (with fat recovery faster than lean tissue recovery) is a cardinal feature of fat overshooting. Within a conceptual framework that integrates the relationship between post-dieting fat overshooting with initial adiposity, the extent of weight loss and the differential lean-fat partitioning during weight loss vs. weight recovery, we describe here a mathematical model of weight cycling to predict the excess fat that could be gained through repeated dieting and multiple weight cycles from a standpoint of body composition autoregulation.

The recovery of body weight after substantial weight loss or growth retardation is often characterized by a disproportionately higher rate of fat mass vs. lean mass recovery, with this phenomenon of "preferential catch-up fat" being contributed by energy conservation (thrifty) metabolism. To test the hypothesis that a low core body temperature (T c ) constitutes a thrifty metabolic trait underlying the high metabolic efficiency driving catch-up fat, the Anipill system, with telemetry capsules implanted in the peritoneal cavity, was used for continuous monitoring of T c for several weeks in a validated rat model of semistarvation-refeeding in which catch-up fat is driven solely by suppressed thermogenesis. In animals housed at 22°C, 24-h T c was reduced in response to semistarvation (-0.77°C, P < 0.001) and remained significantly lower than in control animals during the catch-up fat phase of refeeding (-0.27°C on average, P < 0.001), the lower T c during refeeding being more pronounced during the light phase than during the dark phase of the 24-h cycle (-0.30°C vs. -0.23°C, P < 0.01) and with no between-group differences in locomotor activity. A lower 24-h T c in animals showing catch-up fat was also observed when the housing temperature was raised to 29°C (i.e., at thermoneutrality). The reduced energy cost of homeothermy in response to caloric restriction persists during weight recovery and constitutes a thrifty metabolic trait that contributes to the high metabolic efficiency that underlies the rapid restoration of the body's fat stores during weight regain, with implications for obesity relapse after therapeutic slimming and the pathophysiology of catch-up growth.

Aim: Sharing a festive meal associated with alcohol is quite common. While the cardiovascular changes occurring after meal ingestion of different nutrient composition has been well-established, the effects of ingesting a festive versus a standard meal accompanied with alcohol are less clear. Here, we compared the postprandial hemodynamics, cutaneous and psychomotor performance responses after ingestion of a classical Swiss festive meal [cheese fondue (CF)] versus a light ready-meal [Nasi Goreng (NG)], both accompanied with white wine. Methods: In a randomized cross over design, we examined in 12 healthy young men, the continuous cardiovascular, cutaneous, and reaction time responses to ingestion of cheese fondue versus a standard meal at rest (sitting position) and hemodynamic changes in response to orthostatic challenge (active standing) in pre- and postprandial phases. Results: Breath alcohol concentration after wine ingestion was similar after both meal types. Compared to the standard meal, consumption of CF induced higher increases in heart rate (HR), cardiac output (CO), double product (DP) and cardiac power output (CPO), greater vasodilation, and rises in skin blood flow and skin temperature. Greater increases in HR, DP, and mean blood pressure (MBP) were observed during orthostatic challenges with CF compared to NG. A two-choice reaction time task revealed similar reaction times with both meals, suggesting no influence of meal composition on psychomotor performance. Conclusion: In sitting position, CF ingestion induced a more important cardiovascular load compared to NG. Although the dose of alcohol and the festive meal used here did not lead to orthostatic hypotension, eating CF induced a greater cardiometabolic load suggesting that hemodynamic reserves have been encroached during active standing. This may impede the cardiovascular capacity during physical exercise or stress situations, particularly in elderly subjects who are at greater risk for postprandial hypotension and cardiovascular diseases., (Copyright © 2019 Sarafian, Charrière, Maufrais and Montani.)

Implementation of efficacious dietary interventions to regulate energy balance requires understanding of the determinants of individual response. To date, information regarding individual variability in response to elevated meal protein content is lacking. This study investigates whether sex and/or oral contraceptive pill (OCP) use play a role in the response to elevated meal protein in 21 healthy young adults (seven men, seven women not taking OCP, and seven women who were OCP users). Participants consumed each of three standardized isocaloric (590 kcal) meals of differing protein content (11, 23, 31% kcal protein). Resting energy expenditure (EE), respiratory quotient (RQ), hunger and satiety were measured at baseline (fasting) and during 180 min postprandial. Whilst significant dose-response increases in EE were observed in men, meal protein-induced EE in women without OCP reached a maximum at <23% protein. Women taking OCP reported lower postprandial fullness than women without OCP, despite similar body size, but also, most notably, no significant difference in EE response between any of the meals. Whilst the mechanisms underpinning this thermogenic inflexibility in response across a wide-range (three-fold) of protein meal content require further investigation, this highlights the need for careful consideration of factors that may influence an individual's metabolic response to dietary interventions aimed at optimising postprandial thermogenesis for body weight regulation.

Objective: The recovery of body composition after weight loss is characterized by an accelerated rate of fat recovery (preferential catch-up fat) resulting partly from an adaptive suppression of thermogenesis. Although the skeletal muscle has been implicated as an effector site for such thrifty (energy conservation) metabolism driving catch-up fat, the underlying mechanisms remain to be elucidated. We test here the hypothesis that this thrifty metabolism driving catch-up fat could reside in a reduced rate of protein turnover (an energetically costly "futile" cycle) and in altered local thyroid hormone metabolism in skeletal muscle. Methods: Using a validated rat model of semistarvation-refeeding in which catch-up fat is driven solely by suppressed thermogenesis, we measured after 1 week of refeeding in refed and control animals the following: (i) in-vivo rates of protein synthesis in hindlimb skeletal muscles using the flooding dose technique of 13 C-labeled valine incorporation in muscle protein, (ii) ex-vivo muscle assay of net formation of thyroid hormone tri-iodothyronine (T3) from precursor hormone thyroxine (T4), and (iii) protein expression of skeletal muscle deiodinases (type 1, 2, and 3). Results: We show that after 1 week of calorie-controlled refeeding, the fractional protein synthesis rate was lower in skeletal muscles of refed animals than in controls (by 30-35%, p < 0.01) despite no between-group differences in the rate of skeletal muscle growth or whole-body protein deposition-thereby underscoring concomitant reductions in both protein synthesis and protein degradation rates in skeletal muscles of refed animals compared to controls. These differences in skeletal muscle protein turnover during catch-up fat were found to be independent of muscle type and fiber composition, and were associated with a slower net formation of muscle T3 from precursor hormone T4, together with increases in muscle protein expression of deiodinases which convert T4 and T3 to inactive forms. Conclusions: These results suggest that diminished skeletal muscle protein turnover, together with altered local muscle metabolism of thyroid hormones leading to diminished intracellular T3 availability, are features of the thrifty metabolism that drives the rapid restoration of the fat reserves during weight regain after caloric restriction.

Increasing lifestyle energy expenditure has long been advocated in the prevention and treatment of obesity, as embodied in the ancient prescription of Hippocrates (the 'father of modern medicine') that people with obesity should eat less and exercise more. However, the long-term outcome of exercise alone or in combination with dieting in obesity management is poor. To understand the reasons underlying these failures and to develop novel strategies that target lifestyle energy expenditure in both prevention and treatment of obesity, research over the past decades has focused on (i) the interactions between physical activity and body weight (and its composition) throughout the lifespan; (ii) the influence of biology and potential compensatory changes in energy expenditure, food intake and food assimilation in response to energy deficits; and (iii) the impact of the built environment (outdoor and indoor) and smart technology on physical activity behaviours, thermoregulatory thermogenesis and metabolic health. It is against this background that recent advances relevant to the theme of 'Targeting Lifestyle Energy Expenditure in the Management of Obesity and Health: From Biology to Built Environment' are addressed in this overview and the nine review articles in this supplement, reporting the proceedings of the 9th Fribourg Obesity Research Conference., (© 2018 World Obesity Federation.)

Type-II l-arginine:ureahydrolase, arginase-II (Arg-II), is abundantly expressed in the kidney. The physiologic role played by Arg-II in the kidney remains unknown. Herein, we report that in mice that are deficient in Arg-II (Arg-II -/- ), total and membrane-associated aquaporin-2 (AQP2) protein levels were significantly higher compared with wild-type (WT) controls. Water deprivation enhanced Arg-II expression, AQP2 levels, and membrane association in collecting ducts. Effects of water deprivation on AQP2 were stronger in Arg-II -/- mice than in WT mice. Accordingly, a decrease in urine volume and an increase in urine osmolality under water deprivation were more pronounced in Arg-II -/- mice than in WT mice, which correlated with a weaker increase in plasma osmolality in Arg-II -/- mice. There was no difference in vasopressin release under water deprivation conditions between either genotype of mice. Although total AQP2 and phosphorylated AQP2-S256 levels (mediated by PKA) in kidneys under water deprivation conditions were significantly higher in Arg-II -/- mice compared with WT animals, there is no difference in the ratio of AQP2-S256:AQP2. In cultured mouse collecting duct principal mCCD cl1 cells, expression of both Arg-II and AQP2 were enhanced by the vasopressin type 2 receptor agonist, desamino- d-arginine vasopressin (dDAVP). Silencing Arg-II enhanced the expression and membrane association of AQP2 by dDAVP without influencing cAMP levels. In conclusion, in vivo and in vitro experiments demonstrate that Arg-II negatively regulates AQP2 and the urine-concentrating capability in kidneys via a mechanism that is not associated with the modulation of the cAMP pathway.-Huang, J., Montani, J.-P., Verrey, F., Feraille, E., Ming, X.-F., Yang, Z. Arginase-II negatively regulates renal aquaporin-2 and water reabsorption.

Aim: Red wine is usually ingested as an unmixed drink. However, mixtures of wine with juices and/or sucrose (mixed wine) are becoming more and more popular and could be ingested at either cold or hot temperature. Although the temperature effects on the cardiovascular system have been described for water and tea, with greater energy expenditure (EE) and lower cardiac workload with a colder drink, little information is available on the impact of temperature of alcoholic beverages on alcoholemia and cardiometabolic parameters. The purpose of the present study was to compare the acute cardiovascular and metabolic changes in response to mixed wine ingested at a cold or at a hot temperature. Methods: In a randomized crossover design, 14 healthy young adults (seven men and seven women) were assigned to cold or hot mixed wine ingestion. Continuous cardiovascular, metabolic, and cutaneous monitoring was performed in a comfortable sitting position during a 30-min baseline and for 120 min after ingesting 400 ml of mixed wine, with the alcohol content adjusted to provide 0.4 g ethanol/kg of body weight and drunk at either cold (3°C) or hot (55°C) temperature. Breath alcohol concentration was measured intermittently throughout the study. Results: Overall, alcoholemia was not altered by drink temperature, with a tendency toward greater values in women compared to men. Early responses to mixed wine ingestion (0-20 min) indicated that cold drink transiently increased mean blood pressure (BP), cardiac vagal tone, and decreased skin blood flow (SkBf) whereas hot drink did not change BP, decreased vagal tone, and increased SkBf. Both cold and hot mixed wine led to increases in EE and reductions in respiratory quotient. Late responses (60-120 min) led to similar cardiovascular and metabolic changes at both drink temperatures. Conclusion: The magnitude and/or the directional change of most of the study variables differed during the first 20 min following ingestion and may be related to drink temperature. By contrast, late changes in cardiometabolic outcomes were similar between cold and hot wine ingestion, underlying the typical effect of alcohol and sugar intake on the cardiovascular system.

Although Switzerland is considered a small country, it has its share in discoveries, inventions and developments for the assessment of energy metabolism. This includes seminal contributions to respiratory and metabolic physiology and to devices for measuring energy expenditure by direct and indirect calorimetry in vivo in humans and small animals (as well as in vitro in organs/tissues), for the purpose of evaluating the basic nutritional requirements. A strong momentum came during World War II when it was necessary to evaluate the energy requirements of soldiers protecting the country by assessing their energy expenditure, as well as to determine the nutritional needs of the Swiss civil population in time of war when food rationing was necessary to ensure national neutrality and independence. A further impetus came in the 1970s at the start of the obesity epidemics, toward a better understanding of the metabolic basis of obesity, ranging from the development of whole-body concepts to molecular mechanisms. In a trip down memory lane, this review focuses on some of the earlier leading Swiss scientists who have contributed to a better understanding of the field.

Aim: Tea is usually consumed at two temperatures (as hot tea or as iced tea). However, the importance of drink temperature on the cardiovascular system and on metabolism has not been thoroughly investigated. The purpose of this study was to compare the cardiovascular, metabolic and cutaneous responses to the ingestion of caffeinated herbal tea (Yerba Mate) at cold or hot temperature in healthy young subjects. We hypothesized that ingestion of cold tea induces a higher increase in energy expenditure than hot tea without eliciting any negative effects on the cardiovascular system. Methods: Cardiovascular, metabolic and cutaneous responses were analyzed in 23 healthy subjects (12 men and 11 women) sitting comfortably during a 30-min baseline and 90 min following the ingestion of 500 mL of an unsweetened Yerba Mate tea ingested over 5 min either at cold (~3°C) or hot (~55°C) temperature, according to a randomized cross-over design. Results: Averaged over the 90 min post-drink ingestion and compared to hot tea, cold tea induced (1) a decrease in heart rate (cold tea: -5 ± 1 beats.min -1 ; hot tea: -1 ± 1 beats.min -1 , p < 0.05), double product, skin blood flow and hand temperature and (2) an increase in baroreflex sensitivity, fat oxidation and energy expenditure (cold tea: +8.3%; hot tea: +3.7%, p < 0.05). Averaged over the 90 min post-drink ingestion, we observed no differences of tea temperature on cardiac output work and mean blood pressure responses. Conclusion: Ingestion of an unsweetened caffeinated herbal tea at cold temperature induced a greater stimulation of thermogenesis and fat oxidation than hot tea while decreasing cardiac load as suggested by the decrease in the double product. Further experiments are needed to evaluate the clinical impact of unsweetened caffeinated herbal tea at a cold temperature for weight control.

Type-II L-arginine:ureahydrolase, arginase-II (Arg-II), is shown to activate mechanistic target of rapamycin complex 1 (mTORC1) pathway and contributes to cell senescence and apoptosis. In an attempt to elucidate the underlying mechanism, we identified myosin-1b (Myo1b) as a mediator. Overexpression of Arg-II induces re-distribution of lysosome and mTOR but not of tuberous sclerosis complex (TSC) from perinuclear area to cell periphery, dissociation of TSC from lysosome and activation of mTORC1-ribosomal protein S6 kinase 1 (S6K1) pathway. Silencing Myo1b prevents all these alterations induced by Arg-II. By overexpressing Myo1b or its mutant with point mutation in its pleckstrin homology (PH) domain we further demonstrate that this effect of Myo1b is dependent on its PH domain that is required for Myo1b-lysosome association. Notably, Arg-II promotes association of Myo1b with lysosomes. In addition, we show that in senescent vascular smooth muscle cells with elevated endogenous Arg-II, silencing Myo1b prevents Arg-II-mediated lysosomal positioning, dissociation of TSC from lysosome, mTORC1 activation and cell apoptosis. Taken together, our study demonstrates that Myo1b mediates the effect of Arg-II in activating mTORC1-S6K1 through promoting peripheral lysosomal positioning, that results in spatial separation and thus dissociation of TSC from lysosome, leading to hyperactive mTORC1-S6K1 signaling linking to cellular senescence/apoptosis.

Recent body composition studies on the island of Mauritius in young adults belonging to the two main ethnicities-Indians (South Asian descent) and Creoles (African/Malagasy descent)-have shown gender-specific ethnic differences in their body mass index (BMI)-Fat% relationships. We investigated here whether potential gender and ethnic differences in blood leptin would persist beyond that explained by differences in body composition. In healthy young adult Mauritian Indians and Creoles (79 men and 80 women; BMI range: 15-41 kg m -2 ), we investigated the relationships between fasted serum leptin with BMI, waist circumference (WC), total fat% assessed by deuterium oxide dilution technique and central adiposity (trunk fat%) assessed by abdominal bioimpedance analysis. The results indicate that the greater elevations in leptin-BMI and leptin-WC regression lines in women compared with men, as well as in Indian men compared with Creole men, are abolished when BMI and WC are replaced by total body fat% and trunk fat%, respectively. In women, no significant between-ethnic difference is observed in total body fat%, trunk fat% and serum leptin. Thus, in young adult Mauritians, a population at high risk for later cardiometabolic diseases, the differences in body fat% entirely accounted for the observed gender and ethnic differences in serum leptin.

Aim: Acute ingestion of alcohol is often accompanied by cardiovascular dysregulation, malaise and even syncope. The full hemodynamic and cutaneous responses to the combination of alcohol and sugar (i.e., alcopops), a common combination in young people, and the mechanisms for the propensity to orthostatic intolerance are not well established. Thus, the purpose of this study was to evaluate the cardiovascular and cutaneous responses to alcopops in young subjects. Methods: Cardiovascular and cutaneous responses were assessed in 24 healthy young subjects (12 men, 12 women) sitting comfortably and during prolonged active standing with a 30-min baseline and 130 min following ingestion of 400 mL of either: water, water + 48 g sugar, water + vodka (1.28 mL.kg -1 of body weight, providing 0.4 g alcohol.kg -1 ), water + sugar + vodka, according to a randomized cross-over design. Results: Compared to alcohol alone, vodka + sugar induced a lower breath alcohol concentration (BrAC), blood pressure and total peripheral resistance ( p < 0.05), a higher cardiac output and heart rate ( p < 0.05) both in sitting position and during active standing. In sitting position vodka + sugar consumption also led to a greater increase in skin blood flow and hand temperature ( p < 0.05) and a decrease in baroreflex sensitivity ( p < 0.05). We observed similar results between men and women both in sitting position and during active standing. Conclusion: Despite lower BrAC, ingestion of alcopops induced acute vasodilation and hypotension in sitting position and an encroach of the hemodynamic reserve during active standing. Even if subjects did not feel any signs of syncope these results could be of clinical importance with higher doses of alcohol or if combined to other hypotensive challenges.

Orthostatic challenge produced by upright posture may lead to syncope if the cardiovascular system is unable to maintain adequate brain perfusion. This review outlines orthostatic intolerance related to the aging process, long-term bedrest confinement, drugs, and disease. Aging-associated illness or injury due to falls often leads to hospitalization. Older patients spend up to 83% of hospital admission lying in bed and thus the consequences of bedrest confinement such as physiological deconditioning, functional decline, and orthostatic intolerance represent a central challenge in the care of the vulnerable older population. This review examines current scientific knowledge regarding orthostatic intolerance and how it comes about and provides a framework for understanding of (patho-) physiological concepts of cardiovascular (in-) stability in ambulatory and bedrest confined senior citizens as well as in individuals with disease conditions [e.g., orthostatic intolerance in patients with diabetes mellitus, multiple sclerosis, Parkinson's, spinal cord injury (SCI)] or those on multiple medications (polypharmacy). Understanding these aspects, along with cardio-postural interactions, is particularly important as blood pressure destabilization leading to orthostatic intolerance affects 3-4% of the general population, and in 4 out of 10 cases the exact cause remains elusive. Reviewed also are countermeasures to orthostatic intolerance such as exercise, water drinking, mental arithmetic, cognitive training, and respiration training in SCI patients. We speculate that optimally applied countermeasures such as mental challenge maintain sympathetic activity, and improve venous return, stroke volume, and consequently, blood pressure during upright standing. Finally, this paper emphasizes the importance of an active life style in old age and why early re-mobilization following bedrest confinement or bedrest is crucial in preventing orthostatic intolerance, falls and falls-related injuries in older persons.

The mitochondrial arginase type II (Arg-II) has been shown to interact with ribosomal protein S6 kinase 1 (S6K1) and mitochondrial p66 Shc and to promote cell senescence, apoptosis and inflammation under pathological conditions. However, the impact of Arg-II on organismal lifespan is not known. In this study, we demonstrate a significant lifespan extension in mice with Arg-II gene deficiency (Arg-II -/- ) as compared to wild type (WT) control animals. This effect is more pronounced in the females than in the males. The gender difference is associated with higher Arg-II expression levels in the females than in the males in skin and heart at both young and old age. Ablation of Arg-II gene significantly reduces the aging marker p16 INK4a levels in these tissues of old female mice, whereas in the male mice this effect of Arg-II deficiency is weaker. In line with this observation, age-associated increases in S6K1 signaling and p66 Shc levels in heart are significantly attenuated in the female Arg-II -/- mice. In the male mice, only p66 Shc but not S6K1 signaling is reduced. In summary, our study demonstrates that Arg-II may play an important role in the acceleration of aging in mice. Genetic disruption of Arg-II in mouse extends lifespan predominantly in females, which relates to inhibition of S6K1, p66 Shc , and p16 INK4a . Thus, Arg-II may represent a promising target to decelerate aging process and extend lifespan as well as to treat age-related diseases.

Objective: There is much interest in the role of dietary protein for weight control. However, there remains a need to characterize individual determinants of the thermogenic effects of protein. This study aimed to investigate the influence of menstrual cycle phase and the combined, monophasic oral contraceptive pill on the thermogenic response to a standardized high-protein (HP) versus normal-protein (NP) meal., Methods: Following an overnight fast, resting energy expenditure (EE) was measured in 16 healthy young women (8 taking and 8 not taking the pill) and 8 men for 30 minutes pre ingestion and 3 hours post ingestion of a NP (11%) or HP (24%) meal., Results: There was no effect of menstrual phase or contraceptive pill use on fasting EE or NP response. However, HP increased EE significantly more than NP in women not taking the oral contraceptive pill and in men, but not in women taking the pill., Conclusions: This study shows an absence of the greater thermic effect of HP versus NP in women taking the oral contraceptive pill and has important implications regarding the effectiveness of HP for body weight regulation in women. With current obesity treatment/prevention strategies remaining largely ineffective, understanding the relationship between oral contraceptive pill use and protein-induced thermogenesis may enable the successful recalibration of existing dietary recommendations., (© 2017 The Obesity Society.)

Purpose: There is increasing interest into the potentially beneficial effects of galactose for obesity and type 2 diabetes management as it is a low-glycemic sugar reported to increase satiety and fat mobilization. However, fructose is also a low-glycemic sugar but with greater blood pressure elevation effects than after glucose ingestion. Therefore, we investigated here the extent to which the ingestion of galactose, compared to glucose and fructose, impacts upon haemodynamics and blood pressure., Methods: In a randomized cross-over study design, 9 overnight-fasted young men attended 3 separate morning sessions during which continuous cardiovascular monitoring was performed at rest for at least 30 min before and 120 min after ingestion of 500 mL of water containing 60 g of either glucose, fructose or galactose. These measurements included beat-to-beat systolic and diastolic blood pressure, heart rate deduced by electrocardiography, and stroke volume derived by impedance cardiography; these measurements were used to calculate cardiac output and total peripheral resistance., Results: Ingestion of galactose, like glucose, led to significantly lesser increases in systolic, diastolic and mean blood pressure than fructose ingestion (p < 0.05). Furthermore, the increase in cardiac output and reduction in total peripheral resistance observed after ingestion of glucose were markedly lower after galactose ingestion (p < 0.01)., Conclusions: Galactose thus presents the interesting characteristics of a low-glycemic sugar with mild cardiovascular effects. Further studies are warranted to confirm the clinical relevance of the milder cardiovascular effects of galactose than other sugars for insulin resistant obese and/or diabetic patients with cardiac insufficiency.

Background: There is increasing interest in the use of pill-sized ingestible capsule telemetric sensors for assessing core body temperature (Tc) as a potential indicator of variability in metabolic efficiency and thrifty metabolic traits. The aim of this study was to investigate the feasibility and accuracy of measuring Tc using the CorTemp ® system., Methods: Tc was measured over an average of 20 h in 27 human subjects, with measurements of energy expenditure made in the overnight fasted state at rest, during standardized low-intensity physical activity and after a 600 kcal mixed meal. Validation of accuracy of the capsule sensors was made ex vivo against mercury and electronic thermometers across the physiological range (35-40°C) in morning and afternoon of 2 or 3 consecutive days. Comparisons between capsule sensors and thermometers were made using Bland-Altman analysis. Systematic bias, error, and temperature drift over time were assessed., Results: The circadian Tc profile classically reported in free-living humans was confirmed. Significant increases in Tc (+0.2°C) were found in response to low-power cycling at 40-50 W (~3-4 METs), but no changes in Tc were detectable during low-level isometric leg press exercise (<2 METs) or during the peak postprandial thermogenesis induced by the 600 kcal meal. Issues of particular interest include fast "turbo" gut transit with expulsion time of <15 h after capsule ingestion in one out of every five subjects and sudden erratic readings in teletransmission of Tc. Furthermore, ex vivo validation revealed a substantial mean bias (exceeding ±0.5°C) between the Tc capsule readings and mercury or electronic thermometers in half of the capsules. When examined over 2 or 3 days, the initial bias (small or large) drifted in excess of ±0.5°C in one out of every four capsules., Conclusion: Since Tc is regulated within a very narrow range in the healthy homeotherm's body (within 1°C), physiological investigations of Tc require great accuracy and precision (better than 0.1°C). Although ingestible capsule methodology appears of great interest for non-invasively monitoring the transit gut temperature, new technology requires a reduction in the inherent error of measurement and elimination of temperature drift and warrants more interlaboratory investigation on the above factors.

Aging is associated with glucose intolerance. Arginase-II (Arg-II), the type-II L -arginine-ureahydrolase, is highly expressed in pancreas. However, its role in regulation of pancreatic β-cell function is not known. Here we show that female (not male) mice deficient in Arg-II (Arg-II -/- ) are protected from age-associated glucose intolerance and reveal greater glucose induced-insulin release, larger islet size and β-cell mass, and more proliferative and less apoptotic β-cells compared with the age-matched wild-type (WT) controls. Moreover, Arg-II is mainly expressed in acinar cells and is upregulated with aging, which enhances p38 mitogen-activated protein kinase (p38 MAPK) activation and release of tumor necrosis factor-α (TNF-α). Accordingly, conditioned medium of isolated acinar cells from old WT (not Arg-II -/- ) mice contains higher TNF-α levels than the young mice and stimulates β-cell apoptosis and dysfunction, which are prevented by a neutralizing anti-TNF-α antibody. In acinar cells, our study demonstrates an age-associated Arg-II upregulation, which promotes TNF-α release through p38 MAPK leading to β-cell apoptosis, insufficient insulin secretion, and glucose intolerance in female rather than male mice., (© 2017 by the American Diabetes Association.)

Standardized approaches to assess human energy expenditure (EE) are well defined at rest and at moderate to high-intensity exercise, but not at light intensity physical activities energetically comparable with those of daily life (i.e., 1.5-4 times the resting EE, i.e., 1.5-4 METs). Our aim was to validate a graded exercise test for assessing the energy cost of low-intensity dynamic work in physically inactive humans, that is, those who habitually do not meet the guidelines for moderate-to-vigorous aerobic physical activity levels. In healthy and inactive young men and women ( n  = 55; aged 18-32 years), EE was assessed in the overnight-fasted state by indirect calorimetry at rest and during graded cycling between 5 and 50W for 5 min at each power output on a bicycle ergometer. Repeatability was investigated on three separate days, and the effect of cadence was investigated in the range of 40-90 rpm. Within the low power range of cycling, all subjects perceived the exercise test as "light" on the Borg scale, the preferred cadence being 60 rpm. A strong linearity of the EE-power relationship was observed between 10 and 50 W for each individual ( r  > 0.98), and the calculation of delta efficiency (DE) from the regression slope indicated that DE was similar in men and women (~29%). DE showed modest inter-individual variability with a coefficient of variation (CV) of 11%, and a low intra-individual variability with a CV of ~ 5%. No habituation or learning effect was observed in DE across days. In conclusion, the assessment of the efficiency of low power cycling by linear regression - and conducted within the range of EE observed for low-intensity movements of everyday life (1.5-4 METs) - extends the capacity for metabolic phenotyping in the inactive population., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Purpose: Due to sedentarity-associated disease risks, there is much interest in methods to increase low-intensity physical activity. In this context, it is widely assumed that altering posture allocation can modify energy expenditure (EE) to impact body-weight regulation and health. However, we have recently shown the existence of two distinct phenotypes pertaining to the energy cost of standing-with most individuals having no sustained increase in EE during steady-state standing relative to sitting comfortably. Here, we investigated whether these distinct phenotypes are related to the presence/absence of spontaneous "weight-shifting", i.e. the redistribution of body-weight from one foot to the other., Methods: Using indirect calorimetry to measure EE in young adults during sitting and 10 min of steady-state standing, we examined: (i) heterogeneity in EE during standing (n = 36); (ii) EE and spontaneous weight-shifting patterns (n = 18); (iii) EE during spontaneous weight-shifting versus experimentally induced weight-shifting (n = 7), and; (iv) EE during spontaneous weight-shifting versus intermittent leg/body displacement (n = 6)., Results: Despite heterogeneity in EE response to steady-state standing, no differences were found in the amount or pattern of spontaneous weight-shifting between the two phenotypes. Whilst experimentally induced weight-shifting resulted in a mean EE increase of only 11% (range: 0-25%), intermittent leg/body displacement increased EE to >1.5 METs in all participants., Conclusions: Although the variability in spontaneous weight-shifting signatures between individuals does not appear to underlie heterogeneity in the energy cost of standing posture maintenance, these studies underscore the fact that leg/body displacement, rather than standing posture alone, is needed to increase EE above the currently defined sedentary threshold.

Background: Augmented arginase-II (Arg-II) is implicated in endothelial senescence and inflammation through a mutual positive regulatory circuit with S6K1. This study was conducted to investigate whether Arg-I, another isoform of arginase that has been also reported to play a role in vascular endothelial dysfunction, promotes endothelial senescence through similar mechanisms., Results: The non-senescent human endothelial cells from umbilical veins (passage 2 to 4) were transduced with empty recombinant adenovirus vector (rAd/CMV) as control or rAd/CMV-Arg-I to overexpress Arg-I. Overexpressing Arg-I promoted eNOS-uncoupling, enhanced senescence markers including p53-S15, p21 and senescence-associated β-galactosidase (SA-β-gal) staining, and increased inflammatory vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) as well as monocyte adhesion to endothelial cells without activating S6K1. All the effects of Arg-I were inhibited by the anti-oxidant N-acetylcysteine (NAC)., Conclusions: Our study demonstrates that Arg-I promotes endothelial senescence and inflammatory responses through eNOS-uncoupling unrelated to activation of the S6K1 pathway.

Among the multitude of dietary and lifestyle behaviours that have been proposed to contribute to the obesity epidemic, those that have generated considerable research scrutiny in the past decade are centred upon sleep behaviours, sedentary behaviours (sitting or lying while awake) and diminished low-level physical activities of everyday life, with each category of behaviours apparently presenting an independent risk for obesity and/or cardiometabolic diseases. These behaviours are highly complex, operate in synergy with each other, disrupt the link between regulation of the circadian clock and metabolic physiology and impact on various components of daily energy expenditure and feeding behaviours to promote obesity and hinder the outcome of obesity therapy. As such, this behavioural triad (nutrition, movement and sleep) presents plenty of scope for intervention and optimization in the context of body weight regulation and lifestyle-related disease prevention. It is against this background that recent advances relevant to the theme of 'Nutrition, Movement & Sleep Behaviors: their interactions in pathways to obesity and cardiometabolic diseases' are addressed in this overview and the nine review articles in this supplement reporting the proceedings of the 8th Fribourg Obesity Research Conference., (© 2017 World Obesity Federation.)

Isometric thermogenesis as applied to human energy expenditure refers to heat production resulting from increased muscle tension. While most physical activities consist of both dynamic and static (isometric) muscle actions, the isometric component is very often essential for the optimal performance of dynamic work given its role in coordinating posture during standing, walking and most physical activities of everyday life. Over the past 75 years, there has been sporadic interest into the relevance of isometric work to thermoregulatory thermogenesis and to adaptive thermogenesis pertaining to body-weight regulation. This has been in relation to (i) a role for skeletal muscle minor tremor or microvibration - nowadays referred to as 'resting muscle mechanical activity' - in maintaining body temperature in response to mild cooling; (ii) a role for slowed skeletal muscle isometric contraction-relaxation cycle as a mechanism for energy conservation in response to caloric restriction and weight loss and (iii) a role for spontaneous physical activity (which is contributed importantly by isometric work for posture maintenance and fidgeting behaviours) in adaptive thermogenesis pertaining to weight regulation. This paper reviews the evidence underlying these proposed roles for isometric work in adaptive thermogenesis and highlights the contention that variability in this neglected component of energy expenditure could contribute to human predisposition to obesity., (© 2017 World Obesity Federation.)

Background and Aims: Global estimates of overweight and obesity prevalence are based on the World Health Organisation (WHO) body mass index (BMI) cut-off values of 25 and 30 kg m - 2 , respectively. To validate these BMI cut-offs for adiposity in the island population of Mauritius, we assessed the relationship between BMI and measured body fat mass in this population according to gender and ethnicity., Methods: In 175 young adult Mauritians (age 20-42 years) belonging to the two main ethnic groups-Indians (South Asian descent) and Creoles (African/Malagasy descent), body weight, height and waist circumference (WC) were measured, total body fat assessed by deuterium oxide (D2O) dilution and trunk (abdominal) fat by segmental bioimpedance analysis., Results: Compared to body fat% predicted from BMI using Caucasian-based equations, body fat% assessed by D2O dilution in Mauritians was higher by 3-5 units in Indian men and women as well as in Creole women, but not in Creole men. This gender-specific ethnic difference in body composition between Indians and Creoles is reflected in their BMI-Fat% relationships, as well as in their WC-Trunk Fat% relationships. Overall, WHO BMI cut-offs of 25 and 30 kg m - 2 for overweight and obesity, respectively, seem valid only for Creole men (~24 and 29.5, respectively), but not for Creole women whose BMI cut-offs are 2-4 units lower (21-22 for overweight; 27-28 for obese) nor for Indian men and women whose BMI cut-offs are 3-4 units lower (21-22 for overweight; 26-27 for obese)., Conclusions: The use of BMI cut-off points for classifying overweight and obesity need to take into account both ethnicity and gender to avoid gross adiposity status misclassification in this population known to be at high risk for type-2 diabetes and cardiovascular diseases. This is particularly of importance in obesity prevention strategies both in clinical medicine and public health.

Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase-II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT) C57BL/6 mice and mice deficient in Arg-II gene (Arg-II -/- ) were fed with either a normal chow (NC) or a high-fat-diet (HFD) for 14 weeks (starting at the age of 7 weeks) to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal reactive oxygen species (ROS) levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II -/- mice. Moreover, mesangial expansion as analyzed by Periodic Acid Schiff (PAS) staining and renal expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg-II -/- mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II -/- mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development.

Globally, the popularity of energy drinks is steadily increasing. Scientific interest in their effects on cardiovascular and cerebrovascular systems in humans is also expanding and with it comes a growing number of case reports of adverse events associated with energy drinks. The vast majority of studies carried out in the general population report effects on blood pressure and heart rate. However, inconsistencies in the current literature render it difficult to draw firm conclusions with regard to the effects of energy drinks on cardiovascular and cerebrovascular variables. These inconsistencies are due, in part, to differences in methodologies, volume of drink ingested, and duration of postconsumption measurements, as well as subject variables during the test. Recent well-controlled, randomized crossover studies that used continuous beat-to-beat measurements provide evidence that cardiovascular responses to the ingestion of energy drinks are best explained by the actions of caffeine and sugar, with little influence from other ingredients. However, a role for other active constituents, such as taurine and glucuronolactone, cannot be ruled out. This article reviews the potentially adverse hemodynamic effects of energy drinks, particularly on blood pressure and heart rate, and discusses the mechanisms by which their active ingredients may interact to adversely affect the cardiovascular system. Research areas and gaps in the literature are discussed with particular reference to the use of energy drinks among high-risk individuals., Competing Interests: 2Author disclosures: EK Grasser, JL Miles-Chan, N Charrière, CR Loonam, AG Dulloo, and J-P Montani, no conflicts of interest., (© 2016 American Society for Nutrition.)

Low-intensity physical activity is increasingly promoted as an alternative to sedentary behavior. However, much research to date has focused on moderate- to vigorous-intensity physical activity, and in particular dynamic work, with the effect of low-intensity isometric exercise (<4 METs) on substrate utilization yet to be explored. Here we investigate the effects of such exercise on respiratory quotient (RQ) and determine the extent of intra- and inter-individual variability in response. Energy expenditure, RQ, and substrate oxidation were measured by ventilated-hood indirect calorimetry at rest and in response to standardized, intermittent, low-level isometric leg-press exercises at 5 loads (+5, +10, +15, +20, +25 kg) in 26 healthy, young adults. Nine participants repeated the experiment on 3 separate days to assess within-subject, between-day variability. There was no significant difference in energy cost and heart rate responses to low-intensity isometric exercise (<2 METs) between men and women. However, a sex difference was apparent in terms of substrate oxidation - with men increasing both fat and carbohydrate oxidation, and women only increasing fat oxidation while maintaining carbohydrate oxidation at baseline, resting levels. This sex difference was repeatable and persisted when substrate oxidation was adjusted for differences in body weight or body composition. Individual variability in RQ was relatively low, with both intra- and inter-individual coefficients of variation in the range of 3%-6% in both sexes. These results suggest that women preferentially increase fat oxidation during low-level isometric exercise. Whether such physical activity could be incorporated into treatment/prevention strategies aimed at optimizing fat oxidation in women warrants further investigation.

Background and Purpose: Energy drinks (EDs) are suspected to induce potential adverse cardiovascular effects and have recently been shown to reduce cerebral blood flow velocity (CBFV) in young, healthy subjects. Gender differences in CBFV in response to EDs have not previously been investigated, despite the fact that women are more prone to cardiovascular disturbances such as neurocardiogenic syncope than men. Therefore, the aim of this study was to explore gender differences in cerebrovascular and cardiovascular responses to EDs., Methods: We included 45 subjects in a retrospective analysis of pooled data from two previous randomized trials carried out in our laboratory with similar protocols. Beat-to-beat blood pressure, impedance cardiography, transcranial Doppler, and end-tidal carbon dioxide (etCO2) measurements were made for at least 20 min baseline and for 80 min following the ingestion of 355 mL of a sugar-sweetened ED. Gender and time differences in cerebrovascular and cardiovascular parameters were investigated., Results: CBFV was significantly reduced in response to ED, with the greatest reduction observed in women compared with men (-12.3 ± 0.8 vs. -9.7 ± 0.8%, P < 0.05). Analysis of variance indicated significant time (P < 0.01) and gender × time (P < 0.01) effects. The percentage change in CBFV in response to ED was independent of body weight and etCO2. No significant gender difference in major cardiovascular parameters in response to ED was observed., Conclusions: ED ingestion reduced CBFV over time, with a greater reduction observed in women compared with men. Our results have potential implications for women ED consumers, as well as high-risk individuals.

Uninephrectomy (UniNX) in rats on a fixed food intake leads to increased lipolysis and a low-grade inflammation with an increased subset of circulating cytokines. Because UniNX ablates renal nerves on the side of the removed kidney, we tested the contribution of unilateral renal denervation in the phenotype of UniNX. We compared Sham-operated controls, left nephrectomy (UniNX) and unilateral left kidney denervation (uDNX) in rats 4 weeks after surgery. uDNX did not affect kidney weight and function. In general, the uDNX phenotype was similar to the UniNX phenotype especially for lipolysis in fat pads and increased low-grade inflammation. uDNX led to decreased fat pad weight and increased hormone sensitive lipase and adipocyte triglyceride lipase mRNA levels in epididymal and inguinal adipose tissue, as well as increased circulating lipolysis markers β-hydroxybutyrate and glycerol. Measured circulating hormones such as leptin, T3 and insulin were similar amongst the three groups. The lipolytic cytokines interferon-gamma and granulocyte macrophage colony stimulating factor were increased in the circulation of both uDNX and UniNX groups. These two cytokines were also elevated in the spleen of both groups, but contrastingly they were decreased in fat pads, liver, and kidneys. Both uDNX and UniNX similarly increased noradrenaline content in fat pads and spleen. Melanocortin 4 receptor mRNA levels were increased in the brains of both uDNX and UniNX compared to Sham and may contribute to increased tissue noradrenaline levels. In addition, the farnesoid x receptor (FXR) may contribute to changes in tissue metabolism and inflammation, as anti-inflammatory FXR was decreased in the spleen but increased in other tissues in uDNX and UniNX compared to Sham. In summary, both uDNX and UniNX in rats promote metabolic and immunological alterations by mechanisms that seem to implicate modification of unilateral renal nerve pathways as well as central and peripheral neural pathways.

Background and Aim: There is increasing recognition about the importance of enhancing energy expenditure (EE) for weight control through increases in low-intensity physical activities comparable with daily life (1.5-4 METS). Whole-body vibration (WBV) increases EE modestly and could present both a useful adjuvant for obesity management and tool for metabolic phenotyping. However, it is unclear whether a "dose-response" exists between commonly-used vibration frequencies (VF) and EE, nor if WBV influences respiratory quotient (RQ), and hence substrate oxidation. We aimed to investigate the EE-VF and RQ-VF relationships across three different frequencies (30, 40, and 50Hz)., Methods: EE and RQ were measured in 8 healthy young adults by indirect calorimetry at rest, and subsequently during side-alternating WBV at one of 3 VFs (30, 40, and 50 Hz). Each frequency was assessed over 5 cycles of intermittent WBV (30s vibration/30s rest), separated by 5 min seated rest. During the WBV participants stood on the platform with knees flexed sufficiently to maintain comfort, prevent transmission of vibration to the upper body, and minimise voluntary physical exertion. Repeatability was assessed across 3 separate days in a subset of 4 individuals. In order to assess any sequence/habituation effect, an additional group of 6 men underwent 5 cycles of intermittent WBV (30s vibration/30s rest) at 40 Hz, separated by 5 min seated rest., Results: Side-alternating WBV increased EE relative to standing, non-vibration levels (+36%, p<0.001). However, no differences in EE were observed across VFs. Similarly, no effect of VF on RQ was found, nor did WBV alter RQ relative to standing without vibration., Conclusion: No relationship could be demonstrated between EE and VF in the range of 30-50Hz, and substrate oxidation did not change in response to WBV. Furthermore, the thermogenic effect of intermittent WBV, whilst robust, was quantitatively small (<2 METS).