Fasting Free Fatty Acid Research Articles

Transgenic zero-erucic and high-oleic mustard oil improves glucose clearance rate, erythrocyte membrane docosahexaenoic acid content and reduces osmotic fragility of erythrocytes in male Syrian golden hamsters

Brassica juncea, the Indian mustard variety has high erucic acid (22:1 n-9) in its oil, which causes several deleterious effects. The Centre for Genetic Manipulation of Crop Plants (India) has developed a zero-erucic and high-oleic acid transgenic mustard variety having 67% oleic acid, which is almost equivalent to that of olive oil, i.e. 71%. Therefore, we assessed its impact on erythrocyte osmotic fragility, fluidity and activities of membrane-bound enzymes and insulin sensitivity. 40 male Syrian golden hamsters of 6–8 weeks age, were divided into five groups, consisting of 8 hamsters in each and fed diet containing any one of the oils, i.e. groundnut (GNO), conventional mustard (OCM), low-erucic mustard (OLM), zero-erucic high-oleic transgenic mustard (OTM) and olive (OLO) at 10% level for 16 weeks. At the end, compared to OLO group, OTM-fed hamsters resisted osmotic shock-induced erythrocyte-haemolysis, which corroborated with higher docosahexaenoic acid (DHA; 22:6 n-3) levels in their erythrocyte membranes. However, it did affect neither the fluidity nor the activities of membrane-bound enzymes. Although fasting plasma glucose, insulin and free fatty acid levels were comparable among the various groups; during glucose challenge, OTM diet-fed animals displayed higher disposal rate of circulatory glucose, without altering the insulin levels, when compared to the conventional mustard; OCM. In conclusion, the consumption of oil from zero-erucic high-oleic transgenic mustard improved the DHA content of erythrocyte membrane, which possibly resisted haemolysis and enhanced glucose clearance during glucose overload. However, it did not affect the activities of erythrocyte membrane-bound enzymes and fluidity compared to olive oil.

Oral Glucose Tolerance Test Glucose Peak Time Is Most Predictive of Prediabetes and Hepatic Steatosis in Obese Girls.

Obese adolescent girls are at increased risk for type 2 diabetes, characterized by defects in insulin secretion and action. We sought to determine if later glucose peak timing (>30 minutes), 1-hour glucose >155 mg/dl, or monophasic pattern of glucose excursion during an oral glucose tolerance test (OGTT) reflect a worse cardiometabolic risk profile. Post-pubertal overweight/obese adolescent girls without diabetes were studied (N = 88; age, 15.2 ± 0.2 years; body mass index percentile, 97.7 ± 0.5). All participants completed an OGTT and body composition measures. Thirty-two girls had a four-phase hyperinsulinemic euglycemic clamp with isotope tracers, vascular imaging, and muscle mitochondrial assessments. Participants were categorized by glucose peak timing (≤30 min = early; >30 min = late), 1-hour glucose concentration (±155 mg/dL) and glucose pattern (monophasic, biphasic). Girls with a late (N = 54) vs earlier peak (n = 34) timing had higher peak glucose (P < 0.001) and insulin (P = 0.023), HbA1c (P = 0.021); prevalence of hepatic steatosis (62% vs 26%; P = 0.003) and lower oral disposition index (P < 0.001) and glucagon-like peptide-1 response (P = 0.037). When classified by 1-hour glucose, group differences were similar to peak timing, but minimal when classified by glucose pattern. In the >155 mg/dL group only, peripheral insulin sensitivity and fasting free fatty acids were worse. A later glucose peak or >155 mg/dL 1-hour glucose predicts metabolic disease risk in obese adolescent girls. This may defect incretin effects and first phase insulin response, and muscle and adipose insulin resistance.

Higher Fasting and Postprandial Free Fatty Acid Levels Are Associated With Higher Muscle Insulin Resistance and Lower Insulin Secretion in Young Non-Obese Women

BackgroundTo assess the relationship of the shape of glucose concentration curve during a standardized meal test to serum free fatty acid (FFA) concentrations, insulin resistance and insulin secretion in young non-obese women.MethodsThirty-five young women had a standardized meal for breakfast with measurement of glucose, insulin and FFA concentrations at 0 (fasting), 30, 60 and 120 min; the areas under the concentration curves were calculated (AUCg, AUCi and AUCffa, respectively). Meal-induced insulin response (MIR) was calculated as the ratio between the incremental insulin and glucose concentrations during the first 30 min of meal tests. In two women (group A), post-breakfast glucose (PBG) returned to levels below fasting plasma glucose (FPG) at 30 min; in 15 and 11 women, PBG returned to levels below FPG at 60 and 120 min (groups B and C, respectively). In the remaining seven women (group D), PBG never fell below FPG.ResultsDespite no difference in fasting insulin and AUCi, fasting FFA, AUCg and AUCffa were the lowest in group A, increased linearly from group B to C and plateaued in group D, whereas MIR might be the highest in group A, decreased from group B to C and plateaued in group D.ConclusionYoung women whose PBG returned to FPG more slowly had higher muscle insulin resistance and lower MIR associated with higher fasting and postprandial FFA levels compared with young women whose PBG returned to baseline more quickly.

Impact of hygiene of housing conditions on performance and health of two pig genetic lines divergent for residual feed intake

Pigs selected for high performance may be more at risk of developing diseases. This study aimed to assess the health and performance of two pig lines divergently selected for residual feed intake (RFI) (low RFI (LRFI) v. high RFI (HRFI)) and housed in two contrasted hygiene conditions (poor v. good) using a 2×2 factorial design (n=40/group). The challenge period (Period 1), started on week zero (W0) when 12-week-old pigs were transferred to good or poor housing conditions. At week 6 (W6), half of the pigs in each group were slaughtered. During a recovery period (Period 2) from W6 to W13 to W14, the remaining pigs (n=20/group) were transferred in good hygiene conditions before being slaughtered. Blood was collected every three (Period 1) or 2 weeks (Period 2) to assess blood indicators of immune and inflammatory responses. Pulmonary lesions at slaughter and performance traits were evaluated. At W6, pneumonia prevalence was greater for pigs housed in poor than in good conditions (51% v. 8%, respectively, P<0.001). Irrespective of hygiene conditions, lung lesion scores were lower for LRFI pigs than for HRFI pigs (P=0.03). At W3, LRFI in poor conditions had the highest number of blood granulocytes (hygiene×line, P=0.03) and at W6, HRFI pigs in poor conditions had the greatest plasma haptoglobin concentrations (hygiene×line, P=0.02). During Period 1, growth rate and growth-to-feed ratio were less affected by poor hygiene in LRFI pigs than in HRFI pigs (hygiene×line, P=0.001 and P=0.02, respectively). Low residual feed intake pigs in poor conditions ate more than the other groups (hygiene×line, P=0.002). Irrespective of the line, fasting plasma glucose concentrations were higher in poor conditions, whereas fasting free fatty acids concentrations were lower than in good conditions. At the end of Period 2, pneumonia prevalence was similar for both housing conditions (39% v. 38%, respectively). During Period 2, plasma protein concentrations were greater for pigs previously housed in poor than in good conditions during Period 1. Immune traits, gain-to-feed ratio, BW gain and feed consumption did not differ during Period 2. Nevertheless, at W12, BW of HRFI previously housed in poor conditions was 13.4 kg lower than BW of HRFI pigs (P<0.001) previously housed in good conditions. In conclusion, health of the most feed efficient LRFI pigs was less impaired by poor hygiene conditions. This line was able to preserve its health, growth performance and its feed ingestion to a greater extent than the less efficient HRFI line.

Does endogenous GLP-1 affect resting energy expenditure and fuel selection in overweight and obese adults?

To investigate the association between fasting glucagon-like peptide 1 (GLP-1) levels and resting energy expenditure (REE), and respiratory quotient (RQ) in overweight and obese adults. Study participants were enrolled at the Dietetic and Metabolic Unit, University of Pavia, Italy. Inclusion criteria were age≥25 and≤45years, and body mass index (BMI)≥25 and≤35kg/m2. Diabetic subjects were excluded. Body composition was measured by dual-energy X-ray absorptiometry. REE was evaluated using indirect calorimetry, and RQ was calculated from respiratory gas exchanges. Fasting GLP-1, glucose, insulin and free fatty acid (FFA) levels, and 24-h norepinephrine urinary excretion were measured. Homeostasis model assessments of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β) were calculated. Thirty-seven participants were included (age 43.4±1.6years; BMI 30.6±0.5kg/m2). REE was not associated with fasting GLP-1 levels (p=0.98) after adjustment for age, sex, fat-free mass (FFM), and fat mass (FM). Similarly, no association was observed between RQ and GLP-1 levels (p=0.95), after adjustment for age, sex, and body fat. In adults subjects with increased adiposity fasting, GLP-1 levels do not seem to play a role in the regulation of energy metabolism and in fuel selection.

Deletion of JNK2 prevents vitamin-D-deficiency-induced hypertension and atherosclerosis in mice

The c-Jun N-terminal kinase 2 (JNK2) signaling pathway contributes to inflammation and plays a key role in the development of obesity-induced insulin resistance and cardiovascular disease. Macrophages are key cells implicated in these metabolic abnormalities. Active vitamin D downregulates macrophage JNK activation, suppressing oxidized LDL cholesterol uptake and foam cell formation and promoting an anti-inflammatory phenotype. To determine whether deletion of JNK2 prevents high blood pressure and atherosclerosis known to be induced by vitamin D deficiency in mice, we generated mice with knockout of JNK2 in a background susceptible to diet-induced atherosclerosis (LDLR−/−). JNK2−/− LDLR−/− and LDLR−/− control mice were fed vitamin D-deficient chow for 8 weeks followed by vitamin D-deficient high fat diet (HFD) for 10 weeks and assessed before and after HFD. There was no difference in fasting glucose, cholesterol, triglycerides, or free fatty acid levels. However, JNK2−/− mice, despite vitamin D-deficient diet, had 20–30mmHg lower systolic (SBP) and diastolic (DBP) blood pressure before HFD compared to control mice fed vitamin D-deficient diets, with persistent SBP differences after HFD. Moreover, deletion of JNK2 reduced HFD-induced atherosclerosis by 30% in the proximal aorta when compared to control mice fed vitamin D-deficient diets. We have previously shown that peritoneal macrophages obtained from LDLR−/− mice fed vitamin D-deficient HFD diets have higher foam cell formation compared to those from mice on vitamin D-sufficient HFD. The increased total cellular cholesterol and modified cholesterol uptake in macrophages from mice on vitamin D-deficient HFD were blunted by deletion of JNK2. These data suggest that JNK2 signaling activation is necessary for the atherosclerosis and hypertension induced by vitamin D deficiency.

Short-term effects of a low carbohydrate diet on glycaemic variables and cardiovascular risk markers in patients with type 1 diabetes: A randomized open-label crossover trial.

The aim of the present study was to assess the effects of a high carbohydrate diet (HCD) vs a low carbohydrate diet (LCD) on glycaemic variables and cardiovascular risk markers in patients with type 1 diabetes. Ten patients (4 women, insulin pump-treated, median ± standard deviation [s.d.] age 48 ± 10 years, glycated haemoglobin [HbA1c] 53 ± 6 mmol/mol [7.0% ± 0.6%]) followed an isocaloric HCD (≥250 g/d) for 1 week and an isocaloric LCD (≤50 g/d) for 1 week in random order. After each week, we downloaded pump and sensor data and collected fasting blood and urine samples. Diet adherence was high (225 ± 30 vs 47 ± 10 g carbohydrates/d; P < .0001). Mean sensor glucose levels were similar in the two diets (7.3 ± 1.1 vs 7.4 ± 0.6 mmol/L; P = .99). The LCD resulted in more time with glucose values in the range of 3.9 to 10.0 mmol/L (83% ± 9% vs 72% ± 11%; P = .02), less time with values ≤3.9 mmol/L (3.3% ± 2.8% vs 8.0% ± 6.3%; P = .03), and less glucose variability (s.d. 1.9 ± 0.4 vs 2.6 ± 0.4 mmol/L; P = .02) than the HCD. Cardiovascular markers were unaffected, while fasting glucagon, ketone and free fatty acid levels were higher at end of the LCD week than the HCD week. In conclusion, the LCD resulted in more time in euglycaemia, less time in hypoglycaemia and less glucose variability than the HCD, without altering mean glucose levels.

Insulin Resistance in Youth Without Diabetes Is Not Related to Muscle Mitochondrial Dysfunction.

Obesity, insulin resistance (IR), and diabetes are increasing in youth, especially in girls. IR is associated with muscle mitochondrial dysfunction in youth and adults with diabetes. However, it is unknown whether this relationship is present in youth prior to development of diabetes. Assess IR and mitochondrial function, including sex differences, in nondiabetic youth. Cross-sectional study of youth in the Exploring Perinatal Outcomes among Children, Resistance to InSulin in Type 1 And Type 2 diabetes, and Androgens and Insulin Resistance Study cohorts. Academic medical university. Two hundred seventy-five youth, 13 to 19 years old [43% males: 17.1 (16.52, 17.63) years, body mass index z-score (BMI-Z) 0.36, 64.7% Tanner 5; 57% females: 17.2 (16.43, 17.67) years, BMI-Z 0.72, 78.9% Tanner 5]. Fasting laboratories, oral glucose tolerance test, and 31P magnetic resonance spectroscopy. IR [triglyceride:high-density lipoprotein (HDL) ratio, Matsuda index, and homeostasis model for insulin resistance (HOMA-IR)] and muscle mitochondrial function (adenosine 5'-diphosphate time constant and oxidative phosphorylation rate). Compared with males, females were more insulin resistant, with higher triglyceride:HDL ratio [1.95 (1.30, 2.79) vs 1.69 (1.21, 2.23), P = 0.042], HOMA-IR [3.18 (2.42, 4.39) vs 2.76 (2.02, 4.08), P = 0.035], and fasting free fatty acids (FFAs) and lower Matsuda score [3.98 (2.71, 5.96) vs 5.39 (3.43, 7.57), P < 0.001]. After adjustment for the higher BMI and Tanner stage and lower physical activity levels seen in females, there were no sex differences in mitochondrial function nor in any IR measure except FFAs. We did not find an association between measures of IR and mitochondrial function. The greater IR seen in adolescent girls vs boys is mostly explained by differences in BMI and physical activity. Mitochondrial function does not appear to be related to IR in a large cohort of nondiabetic youth.

Two weeks of moderate-intensity continuous training, but not high-intensity interval training, increases insulin-stimulated intestinal glucose uptake.

Similar to muscles, the intestine is also insulin resistant in obese subjects and subjects with impaired glucose tolerance. Exercise training improves muscle insulin sensitivity, but its effects on intestinal metabolism are not known. We studied the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on intestinal glucose and free fatty acid uptake from circulation in humans. Twenty-eight healthy, middle-aged, sedentary men were randomized for 2 wk of HIIT or MICT. Intestinal insulin-stimulated glucose uptake and fasting free fatty acid uptake from circulation were measured using positron emission tomography and [18F]FDG and [18F]FTHA. In addition, effects of HIIT and MICT on intestinal GLUT2 and CD36 protein expression were studied in rats. Training improved aerobic capacity (P = 0.001) and whole body insulin sensitivity (P = 0.04), but not differently between HIIT and MICT. Insulin-stimulated glucose uptake increased only after the MICT in the colon (HIIT = 0%; MICT = 37%) (P = 0.02 for time × training) and tended to increase in the jejunum (HIIT = -4%; MICT = 13%) (P = 0.08 for time × training). Fasting free fatty acid uptake decreased in the duodenum in both groups (HIIT = -6%; MICT = -48%) (P = 0.001 time) and tended to decrease in the colon in the MICT group (HIIT = 0%; MICT = -38%) (P = 0.08 for time × training). In rats, both training groups had higher GLUT2 and CD36 expression compared with control animals. This study shows that already 2 wk of MICT enhances insulin-stimulated glucose uptake, while both training modes reduce fasting free fatty acid uptake in the intestine in healthy, middle-aged men, providing an additional mechanism by which exercise training can improve whole body metabolism.NEW & NOTEWORTHY This is the first study where the effects of exercise training on the intestinal substrate uptake have been investigated using the most advanced techniques available. We also show the importance of exercise intensity in inducing these changes.

Role of Adipose Tissue Insulin Resistance in the Natural History of Type 2 Diabetes: Results From the San Antonio Metabolism Study.

In the transition from normal glucose tolerance (NGT) to type 2 diabetes mellitus (T2DM), the role of β-cell dysfunction and peripheral insulin resistance (IR) is well established. However, the impact of dysfunctional adipose tissue has not been fully elucidated. The aim of this study was to evaluate the role of resistance to the antilipolytic effect of insulin (adipose tissue IR [Adipo-IR]) in a large group of subjects with NGT, impaired glucose tolerance (IGT), and T2DM. Three hundred two subjects with varying glucose tolerance received an oral glucose tolerance test (OGTT) and euglycemic insulin clamp. We evaluated Adipo-IR (fasting and mean OGTT plasma free fatty acid [FFA] × insulin concentrations), peripheral IR (1/[Matsuda index] and (M/I)-1 value), and β-cell function (calculated as the ratio of the increment in plasma insulin to glucose [OGTT/IR (ΔI/ΔG ÷ IR)]). Fasting Adipo-IR was increased twofold in obese subjects with NGT and IGT versus lean subjects with NGT (8.0 ± 1.1 and 9.2 ± 0.7 vs. 4.1 ± 0.3, respectively) and threefold in subjects with T2DM (11.9 ± 0.6; P < 0.001). Progressive decline in ΔI/ΔG ÷ IR was associated with a progressive impairment in FFA suppression during OGTT, whereas the rise in mean plasma glucose concentration only became manifest when subjects became overtly diabetic. The progressive decline in β-cell function that begins in individuals with NGT is associated with a progressive increase in FFA and fasting Adipo-IR.

Glucose tolerance and free fatty acid metabolism in adults with variations in TCF7L2 rs7903146

ObjectiveTCF7L2 variant rs7903146 is associated with increased risk for type 2 diabetes. We investigated the effect of TCF7L2 variant rs7903146 and glucose tolerance on free fatty acid (FFA) metabolism. Research Design and MethodsWe recruited 120 individuals, half homozygous for the major CC allele and half homozygous for the minor TT allele at rs7903146; each underwent a 2-h, 75g oral glucose tolerance test (OGTT). Plasma glucose, insulin and free fatty acid concentrations were measured on blood collected before and during the OGTT. ResultsTotal FFA concentrations and percent FA species during OGTT were not different in CC and TT carriers when males and females were considered together. However, monounsaturated fatty acid (MUFA) concentrations and percentages were greater in TT than CC females during the OGTT. TT carriers with high HOMA-IR had significantly greater fasting FFA concentrations, lower disposition index (DI) and greater AUC of glucose than high HOMA-IR CC carriers, whereas no such differences were observed in the low HOMA-IR group. We found that fasting (826±25 vs. 634±22μmol/L, P<0.0001) and OGTT plasma FFA concentrations were greater in IGT than NGT subjects, and the difference remained after adjusting for sex, age, BMI, and genotype. Finally, IGT subjects had greater MUFA concentrations and percentages than NGT subjects during OGTT. ConclusionsDespite similar fasting insulin and glucose, fasting plasma FFA are greater in IGT than NGT adults. Insulin resistance and sex influence plasma FFA responses amongst carriers of the minor T allele of TCF7L2 rs7903146.

Left ventricular vascular and metabolic adaptations to high‐intensity interval and moderate intensity continuous training: a randomized trial in healthy middle‐aged men

High-intensity interval training (HIIT) has become popular, time-sparing alternative to moderate intensity continuous training (MICT), although the cardiac vascular and metabolic effects of HIIT are incompletely known. We compared the effects of 2-week interventions with HIIT and MICT on myocardial perfusion and free fatty acid and glucose uptake. Insulin-stimulated myocardial glucose uptake was decreased by training without any significantly different response between the groups, whereas free fatty acid uptake remained unchanged. Adenosine-stimulated myocardial perfusion responded differently to the training modes (change in mean HIIT: -19%; MICT: +9%; P=0.03 for interaction) and was correlated with myocardial glucose uptake for the entire dataset and especially after HIIT training. HIIT and MICT induce similar metabolic and functional changes in the heart, although myocardial vascular hyperaemic reactivity is impaired after HIIT, and this should be considered when prescribing very intense HIIT for previously untrained subjects. High-intensity interval training (HIIT) is a time-efficient way of obtaining the health benefits of exercise, although the cardiac effects of this training mode are incompletely known. We compared the effects of short-term HIIT and moderate intensity continuous training (MICT) interventions on myocardial perfusion and metabolism and cardiac function in healthy, sedentary, middle-aged men. Twenty-eight healthy, middle-aged men were randomized to either HIIT or MICT groups (n=14 in both) and underwent six cycle ergometer training sessions within 2weeks (HIIT session: 4-6×30s all-out cycling/4min recovery, MICT session 40-60min at 60% V̇O2 peak ). Cardiac magnetic resonance imaging (CMRI) was performed to measure cardiac structure and function and positron emission tomography was used to measure myocardial perfusion at baseline and during adenosine stimulation, insulin-stimulated glucose uptake (MGU) and fasting free fatty acid uptake (MFFAU). End-diastolic and end-systolic volumes increased and ejection fraction slightly decreased with both training modes, although no other changes in CMRI were observed. MFFAU and basal myocardial perfusion remained unchanged. MGU was decreased by training (HIIT from 46.5 to 35.9; MICT from 47.4 to 44.4mmol100g-1 min-1 , P=0.007 for time, P=0.11 for group×time). Adenosine-stimulated myocardial perfusion responded differently to the training modes (change in mean HIIT: -19%; MICT: +9%; P=0.03 for group×time interaction). HIIT and MICT induce similar metabolic and functional changes in the heart, although myocardial vascular hyperaemic reactivity is impaired after HIIT. This should be taken into account when prescribing very intense HIIT for previously untrained subjects.

Influence of New Modified Biliopancreatic Diversion on Blood Glucose and Lipids in GK rats.

This study aimed to investigate the influence of new biliopancreatic diversion (NBPD) and duodenal-jejunal bypass (DJB) surgery on blood glucose, lipids, gastrointestinal hormones, and insulin in Goto-Kakizaki (GK) rats, an animal model for type 2 diabetes, in order to elucidate the mechanisms underlying the therapeutic effect of these types of surgery on this clinical condition. Thirty 30 male GK rats (SPF) aged 12weeks were randomly assigned into three groups (n = 10 per group): sham group, NBPD group, and DJB group. Body weight, random plasma glucose, fasting plasma glucose (FPG), oral glucose tolerance (OGT), blood lipids, plasma insulin, glucagon like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) were measured before and after surgery. NBPD surgery improved glucose tolerance, decreased fasting free fatty acids, triglycerides, and cholesterol. It also increased fasting and postprandial GIP, but caused no change in GLP-1. DJB surgery produced results similar to NBPD surgery except for causing a decrease in postprandial GLP-1 and insulin, and a larger increase in fasting GIP. Moving the biliopancreatic duct outlet to the mid-jejunum (NBPD surgery) improves glucose tolerance and increases GIP, but does not change GLP-1. Adding duodenal bypass (DJB surgery) increases fasting GIP and decreases postprandial GLP-1.

Effect of exercise training on liver function in adults who are overweight or exhibit fatty liver disease: a systematic review and meta-analysis

ObjectiveExercise training has been shown to have beneficial effects on liver function in adults overweight or with fatty liver disease. To establish which exercise programme characteristics were likely to elicit...

Exercise Preserves Fat-free Mass, Submaximal Performance, And Well-being During Short-term Energy Deficiency

The effects of energy deficiency (ED) on health-related outcomes are well described in the literature. Few studies have addressed the effect of controlled ED on performance, and particularly whether exercise (EX), which is known to preserve lean mass, can offset potential declines in performance during ED. PURPOSE: 1) To determine the effects of short-term ED on performance and metabolism and 2) to compare if these effects vary when ED is achieved through caloric restriction (CR) alone or through CR and EX. METHODS: Six young, healthy, and physically fit men (25.2±2.4 y; 79.7±7.7 kg; 9.6±1.5% body fat) participated in this 4-way crossover study. ED conditions were characterized by an energy availability (EA) of 15 kcal/kg fat free mass (FFM), once accomplished via CR to 30 kcal/kg FFM and prescribed EX (15 kcal/kg FFM; ED+EX) and once via CR and no EX (ED-EX). Control conditions were characterized by an EA of 40 kcal/kg FFM, accomplished both with (C+EX) and without EX (C-EX). Conditions lasted 4 days. Body composition, substrate metabolism, aerobic and anaerobic performance, strength, and indices of well-being were measured before and after each condition. RESULTS: Body weight decreased in ED+EX (-1.8±0.4 kg, p=0.004) and ED-EX (-2.4±0.3 kg, p<0.001); whereas FFM decreased only in ED-EX (p=0.06). No significant changes were found in anaerobic performance, leg curl, and leg extension. Bench press performance decreased only in ED+EX (p=0.04). VO2max increased by 6.2±1.7% in ED+EX (p=0.007), but not in ED-EX. Submaximal HR and RPE increased only in ED-EX (p≤0.05). Fasting glucose decreased in ED+EX (-11.9±2.3% p=0.008), but not in ED-EX. In both ED conditions, there was an increase in fasting free fatty acids (ED+EX: 96±25%, p=0.02; ED-EX: 175±98%, p=0.07) and submaximal fat oxidation (ED+EX: 129±51%, p=0.004; ED-EX: 126±21%, p = 0.001). In ED-EX, but not in ED+EX, there was a decrease in positive mood (p=0.04), self-confidence (p=0.02), sense of fitness (p=0.08), physical energy (p=0.06), and recovery (p=0.07). CONCLUSIONS: Despite similar changes in body weight and substrate metabolism during both ED conditions, reductions in FFM, submaximal performance indices, and indices of well-being were only observed in ED-EX. EX seems to be an effective means to maintain performance, FFM, and well-being during short-term ED.

Adipose Insulin Resistance in Obese Adolescents Across the Spectrum of Glucose Tolerance.

Adipocytes represent an important insulin-responsive tissue taking an active part in glucose metabolism. This study sought to assess adipose tissue insulin resistance (IR) across the spectrum of glucose tolerance and to test its relation with free fatty acid (FFA) suppression during an oral glucose tolerance test (OGTT). A cross-sectional analysis of a pediatric clinic-derived cohort of obese adolescents. Participants age 7-20 y with a body mass index that exceeded the 95th percentile for their age and sex. A standard oral glucose tolerance test. The adipose tissue insulin resistance index (calculated as the product of fasting insulin and FFA concentrations) (Adipose IR) and the area under curve of FFAs during the OGTT were compared between glucose tolerance categories. A total of 962 obese children and adolescents participated in this study. Adipose IR significantly increased across glucose tolerance categories (P for trend < .001). Within the normal glucose tolerance participants, an increase in adipose IR was observed related to an increase in 2-hr glucose levels. In a subsample of participants who underwent abdominal imaging for determination of lipid partitioning (n = 115), a tight relation of visceral fat (r = 0.34; P < .001) and the visceral/sc fat ratio (r = 0.55; P < .001) with the Adipose IR index was evident. Greater area under the curve FFAs (lower FFA suppression) during the OGTT was evident with worsening glucose tolerance (P for trend < .001). Glucose tolerance category, degree of obesity (body mass index-z score), IL-6, and low adiponectin emerged as significant predictors of the Adipose IR. Adipose IR is associated with reduced suppression of FFAs during the OGTT and with an altered adipocytokine profile. The negative relation with insulin secretion deserves further longitudinal investigation in the context of deteriorating glucose tolerance.

Intermedin/adrenomedullin 2 polypeptide promotes adipose tissue browning and reduces high-fat diet-induced obesity and insulin resistance in mice

There is an urgent need to develop interventions and policies to mitigate the health effects of obesity by targeting its metabolic mediators. Adrenomedullin 2 (AM2)/intermedin (IMD) is a secreted peptide that has an important role in protecting the cardiovascular system. However, the role of AM2 in type 2 diabetes is unknown. Wild-type (WT) and aP2/AM2 transgenic (aAM2-tg) mice were fed a high-fat diet (HFD) for 8 weeks, and WT mice were treated with AM2 through mini-osmotic pumps. Indirect calorimetry, ambulatory activity and food intake, hyperinsulinemic-euglycemic clamp test, glucose and insulin tolerance tests were used for assessing insulin resistance. Rat primary adipocytes and pre-adipocyte-derived adipocytes were used for in vitro experiments. Real-time PCR and western blot were used for analyses of gene expression and protein level. AM2 and receptor activity-modifying proteins expressions were significantly decreased in the adipose tissue of obese mice. AM2 treatment significantly reduced blood glucose, fasting serum insulin and free fatty acid levels, improved glucose tolerance and insulin sensitivity, and increased the glucose infusion rate during a hyperinsulinemic-euglycemic clamp test, indicating ameliorated HFD-induced insulin resistance. These effects were consistently observed in aAM2-tg mice under HFD conditions, whereas the aAM2-tg mice showed less weight gain and improved glucose tolerance and insulin sensitivity. More importantly, the aAM2-tg mice had increased oxygen consumption and CO2 production, reflecting more energy expenditure. These effects may be due to increased AMP-activated protein kinase phosphorylation and reduced peroxisome proliferator-activated receptor gamma co-activator 1α (PGC1α) acetylation, which result in interactions between PGC1α and PR domain containing 16 and then promote uncoupling protein 1 (UCP1) expression in adipocytes. These results indicate that endogenous AM2 might be involved in energy metabolism in adipocytes through the upregulation of UCP1 expression.

Salvianolic Acid B Ameliorates Hyperglycemia and Dyslipidemia in db/db Mice through the AMPK Pathway

Background/Aims: Salvianolic acid B (Sal B), a major polyphenolic compound of Salvia miltiorrhiza Bunge, has been shown to possess potential antidiabetic activities. However, the action mechanism of SalB in type 2 diabetes has not been investigated extensively. The present study was designed to investigate the effects of Sal B on diabetes-related metabolic changes in a spontaneous model of type 2 diabetes, as well as its potential molecular mechanism. Methods: Male C57BL/KsJ-db/db mice were orally treated with Sal B (50 and 100 mg/kg) or metformin (positive drug, 300 mg/kg) for 6 weeks. Results: Both doses of Sal B significantly decreased fasting blood glucose, serum insulin, triglyceride and free fatty acid levels, reduced hepatic gluconeogenic gene expression and improved insulin intolerance in db/db mice. High dose Sal B also significantly improved glucose intolerance, increased hepatic glycolytic gene expression and muscle glycogen content, and ameliorated histopathological alterations of pancreas, similar to metformin. Sal B treatment resulted in increased phosphorylated AMP-activated protein kinase (p-AMPK) protein expression in skeletal muscle and liver, increased glucose transporter 4 (GLUT4) and glycogen synthase protein expressions in skeletal muscle, and increased peroxisome proliferator-activated receptor alpha (PPARα) and phosphorylated acetyl CoA carboxylase (p-ACC) protein expressions in liver. Conclusion: Our data suggest that Sal B displays beneficial effects in the prevention and treatment of type 2 diabetes at least in part via modulation of the AMPK pathway.

Acute Effects of Linagliptin on Progenitor Cells, Monocyte Phenotypes, and Soluble Mediators in Type 2 Diabetes.

Circulating cells, including endothelial progenitor cells (EPCs) and monocyte subtypes, are involved in diabetic complications. Modulation of these cells may mediate additional benefits of glucose-lowering medications. We assessed whether the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin acutely modifies EPCs and monocyte subsets in patients with type 2 diabetes. This was a randomized, crossover, placebo-controlled trial. The study was conducted at a tertiary referral diabetes outpatient clinic. Forty-six type 2 diabetes patients with (n = 18) or without (n = 28) chronic kidney disease (CKD) participated in the study. Intervention included a 4-day treatment with linagliptin 5 mg or placebo during two arms separated by a 2-week washout. Before and after each treatment, we determined the levels of circulating progenitor cells (CD34, CD133, KDR) and monocyte subtypes (CD14/CD16, chemokine and scavenger receptors) and the concentrations of soluble mediators. Compared with placebo, linagliptin increased CD34(+)CD133(+) progenitor cells (placebo subtracted effect 40.4 ± 18.7/10(6); P = .036), CD34(+)KDR(+) EPCs (placebo subtracted effect 22.1 ± 10.2/10(6); P = .036), and CX3CR1(bright) monocytes (placebo subtracted effect 1.7 ± 0.8%; P = .032). Linagliptin abated DPP-4 activity by greater than 50%, significantly increased active glucagon-like peptide-1 and stromal cell-derived factor-1α, and reduced monocyte chemotactic protein-1, CCL22, and IL-12. Patients with CKD, as compared with those without, had lower baseline CD133(+) and CD34(+)CD133(+) cells and had borderline reduced CD34(+) and CD34(+)KDR(+) cells. The effects of linagliptin on progenitor cells and monocyte subtypes were similar in patients with or without CKD. Fasting plasma glucose, triglycerides and free fatty acids were unaffected. DPP-4 inhibition with linagliptin acutely increases putative vasculoregenerative and antiinflammatory cells. Direct effects of DPP-4 inhibition may be important to lower vascular risk in diabetes, especially in the presence of CKD.

Protein source in a high-protein diet modulates reductions in insulin resistance and hepatic steatosis in fa/fa Zucker rats.

High-protein diets are being promoted to reduce insulin resistance and hepatic steatosis in metabolic syndrome. Therefore, the effect of protein source in high-protein diets on reducing insulin resistance and hepatic steatosis was examined. Fa/fa Zucker rats were provided normal-protein (15% of energy) casein, high-protein (35% of energy) casein, high-protein soy, or high-protein mixed diets with animal and plant proteins. The high-protein mixed diet reduced area under the curve for insulin during glucose tolerance testing, fasting serum insulin and free fatty acid concentrations, homeostatic model assessment index, insulin to glucose ratio, and pancreatic islet cell area. The high-protein mixed and the high-protein soy diets reduced hepatic lipid concentrations, liver to body weight ratio, and hepatic steatosis rating. These improvements were observed despite no differences in body weight, feed intake, or adiposity among high-protein diet groups. The high-protein casein diet had minimal benefits. A high-protein mixed diet was the most effective for modulating reductions in insulin resistance and hepatic steatosis independent of weight loss, indicating that the source of protein within a high-protein diet is critical for the management of these metabolic syndrome parameters.