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ObjectiveThe role of metabolic condition and diet in regulating circulating levels of adropin, a peptide hormone linked to cardiometabolic control, is not well understood. In this study, weight loss and diet effects on plasma adropin concentrations were examined.MethodsThis report includes data from (1) a weight loss trial, (2) an evaluation of acute exercise effects on mixed-meal (60% kcal from carbohydrates) tolerance test responses, and (3) a meta-analysis to determine normal fasting adropin concentrations.ResultsDistribution of plasma adropin concentrations exhibited positive skew and kurtosis. The effect of weight loss on plasma adropin concentrations was dependent on baseline plasma adropin concentrations, with an inverse association between baseline and a decline in concentrations after weight loss (Spearman's ρ = -0.575; P < 0.001). When ranked by baseline plasma adropin concentrations, only values in the upper quartile declined with weight loss. Plasma adropin concentrations under the main area of the bell curve correlated negatively with habitual carbohydrate intake and plasma lipids. There was a negative correlation between baseline values and a transient decline in plasma adropin during the mixed-meal tolerance test.ConclusionsPlasma adropin concentrations in humans are sensitive to dietary macronutrients, perhaps due to habitual consumption of carbohydrate-rich diets suppressing circulating levels. Very high adropin levels may indicate cardiometabolic conditions sensitive to weight loss.

BACKGROUND. Insulin is a key regulator of metabolic function. The effects of excess adiposity, insulin resistance, and hepatic steatosis on the complex integration of insulin secretion and hepatic and extrahepatic tissue extraction are not clear. METHODS. A hyperinsulinemic-euglycemic clamp and a 3-hour oral glucose tolerance test were performed to evaluate insulin sensitivity and insulin kinetics after glucose ingestion in 3 groups: (a) lean subjects with normal intrahepatic triglyceride (IHTG) and glucose tolerance (lean-NL; n = 14), (b) obese subjects with normal IHTG and glucose tolerance (obese-NL; n = 24), and (c) obese subjects with nonalcoholic fatty liver disease (NAFLD) and prediabetes (obese-NAFLD; n = 22). RESULTS. Insulin sensitivity progressively decreased and insulin secretion progressively increased from the lean-NL to the obese-NL to the obese-NAFLD groups. Fractional hepatic insulin extraction progressively decreased from the lean-NL to the obese-NL to the obese-NAFLD groups, whereas total hepatic insulin extraction (molar amount removed) was greater in the obese-NL and obese-NAFLD subjects than in the lean-NL subjects. Insulin appearance in the systemic circulation and extrahepatic insulin extraction progressively increased from the lean-NL to the obese-NL to the obese-NAFLD groups. Total hepatic insulin extraction plateaued at high rates of insulin delivery, whereas the relationship between systemic insulin appearance and total extrahepatic extraction was linear. CONCLUSION. Hyperinsulinemia after glucose ingestion in obese-NL and obese-NAFLD is due to an increase in insulin secretion, without a decrease in total hepatic or extrahepatic insulin extraction. However, the liver's maximum capacity to remove insulin is limited because of a saturable extraction process. The increase in insulin delivery to the liver and extrahepatic tissues in obese-NAFLD is unable to compensate for the increase in insulin resistance, resulting in impaired glucose homeostasis. TRIAL REGISTRATION. ClinicalTrials.gov NCT02706262. FUNDING. NIH grants DK56341 (Nutrition Obesity Research Center), DK052574 (Digestive Disease Research Center), RR024992 (Clinical and Translational Science Award), and T32 DK007120 (a T32 Ruth L. Kirschstein National Research Service Award); the American Diabetes Foundation (1-18-ICTS-119); Janssen Research & Development; and the Pershing Square Foundation., Introduction Obesity is associated with nonalcoholic fatty liver disease (NAFLD), multiorgan insulin resistance, and hyperinsulinemia, which are major risk factors for both type 2 diabetes and coronary heart disease (1-4). [...]

Training at low intensities with moderate vascular occlusion results in increased muscle hypertrophy, strength, and endurance. Elastic knee wraps, applied to the proximal portion of the target muscle, might elicit a stimulus similar to the KAATSU Master Apparatus. The purpose of this study was to test the hypothesis that intermittently occluding the leg extensors with elastic knee wraps would increase whole-blood lactate (WBL) over control (CON). Twelve healthy men and women participated in this study (age 21.2 [+ or -] 0.35 years, height 168.9 [+ or -] 2.60 cm, and body mass 71.2 [+ or -] 4.16 kg). One repetition maximum (1RM) testing for the leg extensors was performed on a leg extension machine for the first trial, followed by occlusion (OCC) and CON trials. Four sets of leg extension exercise (3015-15-15) were completed with 150-second rest between sets at 30% 1RM. Whole-blood lactate, heart rate (HR), and ratings of perceived exertion (RPEs) were measured after every set of exercise and 3 minutes postexercise. Data were analyzed using repeated-measures analysis of variance with statistical significance set at p [less than or equal to] 0.05. Whole-blood lactate increased in response to exercise (p = 0.01) but was not different between groups (OCC 6.28 [+ or -] 0.66 vs. CON 5.35 [+ or -] 0.36 mmol x [L.sup.-1], p = 0.051). Heart rate (OCC 128.86 [+ or -] 4.37 vs. CON 119.72 [+ or -] 4.10 b x [min.sup.-1]) was higher with OCC from sets 2-4 (p [less than or equal to] 0.03), with no difference 3 minutes postexercise (p = 0.29). Rating of perceived exertion was higher with OCC after every set (OCC 15.10 [+ or -] 0.31 vs. CON 12.16 [+ or -] 0.50, p = 0.01 ). In conclusion, no differences exist for WBL between groups, although there was a trend for higher levels with OCC. The current protocol for practical occlusion did not significantly increase metabolic stress more than normal low-intensity exercise. This study does not support the use of knee wraps as a mode of blood-flow restriction. KEY WORDS whole-blood lactate, hypertrophyl muscle, occlusion training

Aerobic capacity/ fitness significantly impacts susceptibility for fatty liver and diabetes, but the mechanisms remain unknown. Herein, we utilized rats selectively bred for high (HCR) and low (LCR) intrinsic aerobic capacity to examine the mechanisms by which aerobic capacity impacts metabolic vulnerability for fatty liver following a 3-day high-fat diet (HFD). Indirect calorimetry assessment of energy metabolism combined with radiolabeled dietary food was employed to examine systemic metabolism in combination with ex vivo measurements of hepatic lipid oxidation. The LCR, but not HCR, displayed increased hepatic lipid accumulation in response to the HFD despite both groups increasing energy intake. However, LCR rats had a greater increase in energy intake and demonstrated greater daily weight gain and percent body fat due to HFD compared with HCR. Additionally, total energy expenditure was higher in the larger LCR. However, controlling for the difference in body weight, the LCR has lower resting energy expenditure compared with HCR. Importantly, respiratory quotient was significantly higher during the HFD in the LCR compared with HCR, suggesting reduced whole body lipid utilization in the LCR. This was confirmed by the observed lower whole body dietary fatty acid oxidation in LCR compared with HCR. Furthermore, LCR liver homogenate and isolated mitochondria showed lower complete fatty acid oxidation compared with HCR. We conclude that rats bred for low intrinsic aerobic capacity show greater susceptibility for dietary-induced hepatic steatosis, which is associated with a lower energy expenditure and reduced whole body and hepatic mitochondrial lipid oxidation. [ABSTRACT FROM AUTHOR]

Individuals with type 2 diabetes (T2D) have poor glycemic control which contributes to cardiovascular disease and other diabetic comorbidities. The often relied upon measures of fasting glucose and glycosylated hemoglobin (HbA1c) do not accurately represent glycemic control because they do not reflect what occurs after meals and throughout the day in the free-living condition. An accumulating body of evidence now suggests that postprandial glucose fluctuations are more tightly correlated with microvascular and macrovascular morbidities and cardiovascular mortality than HbA1c or fasting glucose, stagnant measure of glycemia. Thus, effective therapies are needed which will improve not only HbA1c and fasting glucose, but also regulation of postprandial glycemia. Further, testing for glycemic control should employ a challenge that simulates the free-living condition to best determine how glucose is regulated after meals and throughout the day. Unlike medications, which generally have a poor effect at improving postprandial glucose, exercise is effective in reducing postprandial glycemic excursions in as little as a few days. However, how this is accomplished and the optimal prescription for reducing postprandial glycemic excursions and maintaining improvements in postprandial glycemic control have yet to be elucidated. Still further, the utility of a mixed meal test in providing the optimal challenge for detecting exercise-induced changes in postprandial glycemic control has value that warrants further investigation. Thus, the purpose of this review is to summarize the literature regarding exercise in treating postprandial glycemia in T2D and to review strengths and weaknesses in the current methodology for assessing changes in glycemic control.

Here, we sought to compare the efficacy of combining exercise and metformin for the treatment of type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) in hyperphagic, obese, type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. OLETF rats (age: 20 wk, hyperglycemic and hyperinsulinemic; n = 10/group) were randomly assigned to sedentary (O-SED), SED plus metformin (O-SED + M; 300 mg·kg(-1)·day(-1)), moderate-intensity exercise training (O-EndEx; 20 m/min, 60 min/day, 5 days/wk treadmill running), or O-EndEx + M groups for 12 wk. Long-Evans Tokushima Otsuka (L-SED) rats served as nonhyperphagic controls. O-SED + M, O-EndEx, and O-EndEx + M were effective in the management of type 2 diabetes, and all three treatments lowered hepatic steatosis and serum markers of liver injury; however, O-EndEx lowered liver triglyceride content and fasting hyperglycemia more than O-SED + M. In addition, exercise elicited greater improvements compared with metformin alone on postchallenge glycemic control, liver diacylglycerol content, hepatic mitochondrial palmitate oxidation, citrate synthase, and β-HAD activities and in the attenuation of markers of hepatic fatty acid uptake and de novo fatty acid synthesis. Surprisingly, combining metformin and aerobic exercise training offered little added benefit to these outcomes, and in fact, metformin actually blunted exercise-induced increases in complete mitochondrial palmitate oxidation and β-HAD activity. In conclusion, aerobic exercise training was more effective than metformin administration in the management of type 2 diabetes and NAFLD outcomes in obese hyperphagic OLETF rats. Combining therapies offered little additional benefit beyond exercise alone, and findings suggest that metformin potentially impairs exercise-induced hepatic mitochondrial adaptations.