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Epidemiological and experimental studies have demonstrated that early postnatal nutrition has been associated with long-term effects on glucose homeostasis in adulthood. Recently, our group demonstrated that undernutrition during early lactation affects the expression and activation of key proteins of the insulin signaling cascade in rat skeletal muscle during postnatal development. To elucidate the molecular mechanisms by which undernutrition during early life leads to changes in insulin sensitivity in peripheral tissues, we investigated the insulin signaling in adipose tissue. Adipocytes were isolated from epididymal fat pads of adult male rats that were the offspring of dams fed either a normal or a protein-free diet during the first 10 days of lactation. The cells were incubated with 100 nM insulin before the assays for immunoblotting analysis, 2-deoxyglucose uptake, immunocytochemistry for GLUT4, and/or actin filaments. Following insulin stimulation, adipocytes isolated from undernourished rats presented reduced tyrosine phosphorylation of IR and IRS-1 and increased basal phosphorylation of IRS-2, Akt, and mTOR compared with controls. Basal glucose uptake was increased in adipocytes from the undernourished group, and the treatment with LY294002 induced only a partial inhibition both in basal and in insulin-stimulated glucose uptake, suggesting an involvement of phosphoinositide 3-kinase activity. These alterations were accompanied by higher GLUT4 content in the plasma membrane and alterations in the actin cytoskeleton dynamics. These data suggest that early postnatal undernutrition impairs insulin sensitivity in adulthood by promoting changes in critical steps of insulin signaling in adipose tissue, which may contribute to permanent changes in glucose homeostasis. undernutrition; glucose transporter 4; insulin signaling

Objectives This study examined the effect of Vitis vinifera grape skin extract (ACH09) on hyperglycaemia and the insulin-signalling cascade in alloxan-treated mice. Methods Glycaemia, serum insulin and Western blot analysis of insulin cascade proteins were evaluated in the gastrocnemius muscles of four groups of adult mice: control, ACH09 (200 mg/kg per day, p.o.), alloxan (300 mg/kg, i.p.) and alloxan + ACH09. Insulin secretion in isolated pancreatic islets was also studied. Key findings Glycaemia values in the alloxan + ACH09 and ACH09 groups were significantly lower than in the alloxan-treated and control groups, respectively. Increased insulin resistance (HOMA index) was observed in the alloxan-treated group but not in the alloxan + ACH09 group. Insulin receptor content and Akt phosphorylation were significantly greater in the alloxan + ACH09 group compared with the alloxan-treated group. The glucose transporter (GLUT-4) content was reduced in alloxan-treated mice compared with the control group, while alloxan + ACH09 and ACH09-treated mice showed a significant increase in GLUT-4 content. ACH09 treatment did not change glucose-induced insulin secretion in isolated pancreatic islets. Conclusions The results suggest that ACH09 has hypoglycaemic and antihyperglycaemic effects that are independent of an increase in insulin release but are probably dependent on an increase in insulin sensitivity resulting from an activation of the insulin-signalling cascade in skeletal muscle. [ABSTRACT FROM AUTHOR]

The study investigated the effects of early life overfeeding on metabolic alterations, heart morphology and left ventricular insulin signaling pathway, mainly the glucose transporters GLUT1, GLUT4 and pAKT/AKT ratio. Wistar rats were overfed using the litter size reduction method. The pups were studies at age of 10 and 21 days. We measured heart GLUT1, GLUT4, AKT and pAKT. Animal weight and length, total body lipid, glycogen content, and the plasma levels of insulin, glucose, total cholesterol and triglycerides were measured. Cardiac hypertrophy was evaluated by heart weight/tibia length ratio. Our results showed that overfed animals were overweight, displayed high total body lipids, insulin, glucose, cholesterol and triglycerides plasma levels, and left ventricular hypertrophy with increasing of pAKT/AKT ratio. Moreover, the heart of overfed animals displayed a precocious translocation of GLUT4 and decreased content of GLUT1. In conclusion, we suggest that overfeeding during lactation might induce metabolic and cardiac alterations early in life, leading to the development of cardiac hypertrophy due anticipated insulin dependence created by earlier GLUT4 heart appearance. [ABSTRACT FROM AUTHOR]

Nutritional transition has contributed to growing obesity, mainly by changing eating habits of the population. The mechanisms by which diet-induced obesity leads to cardiac injury are not completely understood, but it is known that obesity is associated to impaired cardiac function and energy metabolism, increasing morbidity and mortality. Therefore, our study aimed to investigate the mechanisms underlying cardiac metabolism impairment related to Western diet-induced obesity. After weaning, male Swiss mice were fed a Western diet for 16 weeks in order to induce obesity. After this period, the content of proteins involved in heart energy metabolism GLUT1, cytosolic lysate and plasma membrane GLUT4, AMPK, pAMPK, IRβ, IRS-1, PGC-1α, CPT1 and UCP2 was evaluated. Also, the oxidative phosphorylation of myocardial fibers was measured by high-resolution respirometry. Mice in the Western diet group (WG) presented altered biometric parameters compared to those in control group, including higher body weight, increased myocardial lipid deposition and glucose intolerance, which demonstrate the obesogenic role of Western diet. WG presented increased CPT1 and UCP2 contents and decreased IRS-1, plasma membrane GLUT4 and PGC-1α contents. In addition, WG presented cardiac mitochondrial dysfunction and reduced biogenesis, demonstrating a lower capacity of carbohydrates and fatty acid oxidation and also decreased coupling between oxidative phosphorylation and adenosine triphosphate synthesis. Cardiac metabolism impairment related to Western diet-induced obesity is probably due to damaged myocardial oxidative capacity, reduced mitochondrial biogenesis and mitochondria uncoupling, which compromise the bioenergetic metabolism of heart., (© 2014.)

Mitochondria are central coordinators of energy metabolism, and changes of their physiology have long been associated with metabolic disorders. Thus, observations of energy dynamics in different cell types are of utmost importance. Therefore, tools with quick and easy handling are needed for consistent evaluations of such interventions. In this paper, our main hypothesis is that during different nutritional situations lymphocytes mitochondrial physiology could be associated with the metabolism of other cell types, such as cardiomyocytes, and consequently be used as metabolic biomarker. Blood lymphocytes and heart muscle fibers were obtained from both fed and 24 h-fasted mice, and mitochondrial analysis was assessed by high-resolution respirometry and western blotting. Carbohydrate-linked oxidation and fatty acid oxidation were significantly higher after fasting. Carnitine palmitoil transferase 1 and uncouple protein 2 contents were increased in the fasted group, while the glucose transporters 1 and 4 and the ratio phosphorylated AMP-activated protein kinase/AMPK did not change between groups. In summary, under a nutritional status modification, mitochondria demonstrated earlier adaptive capacity than other metabolic sensors such as glucose transporters and AMPK, suggesting the accuracy of mitochondria physiology of lymphocytes as biomarker for metabolic changes.

Maternal nutritional environmental in early life has been often associated with long term effects on the immune response in adulthood. The effects of maternal protein deprivation during early lactation on neutrophil-mediated innate immunity were investigated in adult rats, offspring of dams fed with a protein-free diet during the first days of lactation (PD), and compared to controls (22% protein diet). Inflamed PD animals showed an inhibited neutrophil migration and an impaired recruitment of leukocytes from bone marrow pool to circulation. In resting conditions, blood neutrophils from PD present reduced phagocytic activity, increased production of O(2) (-) and NO, basal iNOS expression and constitutive NF-kappaB activation. Moreover, PD rats also show high circulating levels of TNF-alpha and increased expression of TNF-alpha mRNA in the spleen and liver. The data indicate that maternal nutritional stress can interfere on the innate immune response in adulthood, imprinting permanent alterations on cytokine production and neutrophil activation.

Background: Adipose tissue-derived hormones are involved in the pathophysiology of eating disorders and other mental disorders. Studies have suggested that the serum leptin/adiponectin ratio is highly correlated with BMI. Furthermore, it is associated with a number of metabolic processes and inflammatory markers that are involved in obesity and mental disorders, such as the physiopathology of binge eating disorder (BED). We investigated whether variations in leptin and adiponectin serum concentrations differed between adult women with and without BED before and after a meal., Methods: The study group was composed of 8 normal weight women (20-25 kg/m2) without BED, 8 obese women (>/=30 kg/m2) with BED, and 7 obese women without BED (non-BED). Blood samples were collected before and after the consumption of a meal composed of 55% carbohydrates, 15% protein, and 30% lipids., Results: Body mass index (p<0.0001), leptin (p<0.0001) and the leptin/adiponectin ratio (p<0.0001) were higher in obese non-BED women than in obese BED and normal weight groups. Adiponectin (p=0.01) concentrations were lower in the obese BED group than in the other groups before and after the meal., Conclusions: The hypoadiponectinemia followed by the altered levels of leptin in obese BED woman may predispose these subjects to an inadequate energy balance, which could promote weight gain and an increased food intake in woman that may contribute to obesity and binge eating in these subjects.