Blocking FSH induces thermogenic adipose tissue and reduces body fat.

Menopause is associated with bone loss and enhanced visceral adiposity. A polyclonal antibody that targets the ß-subunit of the pituitary hormone follicle-stimulating hormone (Fsh) increases bone mass in mice. Here, we report that this antibody sharply reduces adipose tissue in wild-type mice, phenocopying genetic haploinsufficiency for the Fsh receptor gene Fshr. The antibody also causes profound beiging, increases cellular mitochondrial density, activates brown adipose tissue and enhances thermogenesis. These actions result from the specific binding of the antibody to the ß-subunit of Fsh to block its action. Our studies uncover opportunities for simultaneously treating obesity and osteoporosis.

High-Intensity Exercise and Carbohydrate Supplementation do not Alter Plasma Visfatin.

The purpose of the study was to examine the effect of high-intensity exercise and carbohydrate supplementation (CHO) on plasma visfatin. On 2 separate days, 10 sprint-trained males (age = 26.4 ± 5.3 yr; Ht = 1.77 ± 0.03 m; Wt = 78.78 ± 9.10 kg; BF% = 13.96 ± 7.28%) completed 4, 3-min bouts of cycling at 50% mean anaerobic power, with 6 min of rest between bouts. On CHO day, subjects ingested 50g of CHO 30 min before exercise. On control day, subjects ingested a sugar-free drink (CON) 30 min before exercise. Blood was drawn before supplementation, 15 min before exercise, before and after each exercise bout, and 15 and 30 min post exercise. Visfatin, glucose, and insulin were determined. Truncal fat was assessed by dual energy x-ray. Visfatin was not significantly different between treatments (CHO vs CON) at any time point (p = 0.163), and was not significantly altered by exercise (p = 0.692). Insulin [25.65 vs 8.35 mU/l, CHO vs CON, respectively] and glucose [138.57 vs 98.10 mg/dl, CHO vs CON, respectively] were significantly elevated after CHO ingestion and remained elevated throughout the first half of exercise. Baseline visfatin was significantly correlated with truncal fat (r2 = 0.7782, p < 0.05). Visfatin was correlated to truncal fat in sprint-trained males, but was not altered by exercise or CHO supplementation.

Obesity indices are predictive of elevated C-reactive protein in long-haul truck drivers.

BACKGROUND: Obesity rates in long-haul truck drivers have been shown to be significantly higher than the general population. We hypothesized that commercial drivers with the highest levels of general obesity and abdominal adiposity would have higher concentrations of high sensitivity C-reactive protein (CRP), a marker of inflammation. METHODS: Survey and anthropometric data were collected from 262 commercial drivers. Weight, circumference measures, and blood analysis for CRP (N = 115) were conducted and compared to National Health and Nutrition Examination Survey (NHANES) data. CRP values were non-normally distributed and logarithmically transformed for statistical analyses. RESULTS: BMI, waist circumference, sagittal abdominal diameter, and CRP were significantly higher than in the general population. Anthropometric indices that included height (BMI, waist-to-height ratio, and sagittal diameter-to-height ratio), were most predictive of CRP values. CONCLUSIONS: Abdominal obesity is prevalent in commercial vehicle drivers and is an important indicator of the presence of inflammation in this population. Am. J. Ind. Med. 59:665-675, 2016. © 2016 Wiley Periodicals, Inc.

Voluntary wheel running selectively augments insulin-stimulated vasodilation in arterioles from white skeletal muscle of insulin-resistant rats.

BACKGROUND: Exercise (RUN) prevents declines in insulin-mediated vasodilation, an important component of insulin-mediated glucose disposal, in rats prone to obesity and insulin resistance. OBJECTIVE: Determine whether RUN (1) improves insulin-stimulated vasodilation after insulin resistance has been established, and (2) differentially affects arterioles from red and white muscle. METHODS: Insulin signaling and vasoreactivity to insulin (1-1000 µIU/mL) were assessed in 2A from the Gw and Gr of SED OLETF rats at 12 and 20 weeks of age (SED12, SED20) and those undergoing RUN (RUN20) or caloric restriction (CR20; to match body weight of RUN) from 12 to 20 weeks. RESULTS: Glucose and insulin responses to i.p. glucose were reduced in RUN20, elevated in SED20 (p < 0.05 vs. SED12), and maintained in CR20. Insulin-stimulated vasodilation was greater in Gw but not Gr, 2As of RUN20 (p < 0.01 vs. all groups), and was improved by ET-1 receptor inhibition in Gw 2As from SED20 and CR20 (p < 0.05). There were no differences in microvascular insulin signaling among groups or muscle beds. CONCLUSIONS: RUN selectively improved insulin-mediated vasodilation in Gw 2As, in part through attenuated ET-1 sensitivity/production, an adaptation that was independent of changes in adiposity and may contribute to enhanced insulin-stimulated glucose disposal.

Examining the Effect of Increased Aerobic Exercise in Moderately Fit Adults on Psychological State and Cognitive Function.

Regular physical exercise can decrease the risk for obesity, diabetes, and cardiovascular disease, increase life expectancy, and promote psychological health and neurocognitive functioning. Cross-sectional studies show that cardiorespiratory fitness level (VO2 max) is associated with enhanced brain health, including improved mood state and heightened cognitive performance. Interventional studies are consistent with these cross-sectional studies, but most have focused on low-fit populations. Few such studies have asked if increasing levels of physical activity in moderately fit people can significantly enhance mood, motivation, and cognition. Therefore, the current study investigated the effects of increasing aerobic exercise in moderately fit individuals on psychological state and cognitive performance. We randomly assigned moderately fit healthy adults, 25-59 years of age, who were engaged in one or two aerobic exercise sessions per week to either maintain their exercise regimen (n = 41) or increase their exercise regimen (i.e., 4-7 aerobic workouts per week; n = 39) for a duration of 3 months. Both before and after the intervention, we assessed aerobic capacity using a modified cardiorespiratory fitness test, and hippocampal functioning via various neuropsychological assessments including a spatial navigation task and the Mnemonic Similarity Task as well as self-reported measures including the Positive and Negative Affect Scale, Beck Anxiety Inventory, State-Trait Anxiety Inventory, Perceived Stress Scale, Rumination Scale, Eating Disorders Examination, Eating Attitudes Test, Body Attitudes Test, and Behavioral Regulation of Exercise Questionnaire. Consistent with our initial working hypotheses, we found that increasing exercise significantly decreased measures of negative affect, including fear, sadness, guilt, and hostility, as well as improved body image. Further, we found that the total number of workouts was significantly associated with improved spatial navigation abilities and body image as well as reduced anxiety, general negative affect, fear, sadness, hostility, rumination, and disordered eating. In addition, increases in fitness levels were significantly associated with improved episodic memory and exercise motivation as well as decreased stress and disordered eating. Our findings are some of the first to indicate that in middle-aged moderately-fit adults, continuing to increase exercise levels in an already ongoing fitness regimen is associated with additional benefits for both psychological and cognitive health.

Effects of Lifestyle Factors on Cognition in Minority Population of Older Adults: A Review.

The onset of dementia and Alzheimer's disease (AD) is projected to expand over the next several decades in the United States as the population ages. However, the cognitive health burden is not equally distributed among the population, as Hispanics and African Americans are at higher risk of AD when compared with Non-Hispanic Whites. There is some evidence to indicate that cognitive decline may be associated with lifestyle factors and that interventions in these domains may prevent or delay this decline. These lifestyle factors include social engagement, physical activity, both aerobic and strength training, dietary intake, sleep and stress. This review summarizes, in general, what is known about the relationship between risk factors and cognition and, in particular what is known about this relationship in minority populations. The results show that the relationship between these risk factors and cognitive decline is stronger for some of the factors such as physical activity and dietary intake and weaker for the other factors depending on what is measured and in what populations. It does appear, however, that the studies in minority populations is limited and warrants more targeted research and interventions.

Loaded inter-set stretch may selectively enhance muscular adaptations of the plantar flexors.

The purpose of this study was to evaluate differences in changes in muscle strength and muscle thickness (MT) of the plantar flexor muscles between traditional resistance training (RT) involving passive rest and RT combined with inter-set stretch in the calf raise exercise. Employing a within-subject design, 21 young, healthy men performed plantar flexion exercises twice per week in both a traditional RT (TRAD) format and combined with a 20-second inter-set stretch (STRETCH). One leg was randomly assigned to the TRAD condition and the contralateral leg performed the STRETCH condition throughout the 8-week study period. Dependent variables included MT of the lateral gastrocnemius (LG), medial gastrocnemius (MG) and the soleus (SOL), and isometric strength of the plantar flexors. Results indicated a potential beneficial hypertrophic effect of STRETCH compared to TRAD for the SOL [0.7 mm, CI90% = (0, 1.6)], while the LG had more ambiguous effects [0.4 mm (-0.4, 1.3)] and MG effects were equivocal [0 mm (-0.6, 0.7)]. In general, LG demonstrated greater standardized growth [z = 1.1 (1, 1.3)] as compared to MG [z = 0.3 (0.2, 0.5)] and SOL [z = 0.3 (0.2, 0.5)]. Measures of isometric strength showed a modest advantage to STRETCH. In conclusion, loaded inter-set stretch may enhance MT of the soleus but effects on the gastrocnemii appear uncertain or unlikely in untrained men; plantar flexor strength appears to be modestly enhanced by the interventional strategy.

Work, physical activity, and metabolic health: Understanding insulin sensitivity of long-haul truck drivers.

BACKGROUND: Long-haul truck drivers are disproportionately exposed to metabolic risk; however, little is known about their metabolic health and the role of physical activity and other risk factors in metabolic outcomes. OBJECTIVE: This study compares truck drivers' insulin sensitivity, and associations between metabolic risk factors and insulin sensitivity, with those of the general population. METHODS: Survey, anthropometric, and biometric data were collected from 115 long-haul truckers, which were then compared to the general population data using the National Health and Nutrition Examination Survey (NHANES) dataset. The quantitative insulin sensitivity check index (QUICKI) was used to estimate insulin sensitivity. RESULTS: Truck drivers had lower QUICKI scores than the general population cohort. Sagittal abdominal diameter and exercise were predictive for QUICKI among combined cohorts. Waist circumference and perceived health were more predictive for QUICKI among truck drivers, and sagittal abdominal diameter and income were more predictive for QUICKI among the general population. CONCLUSIONS: Long-haul truckers appear to represent a subset of the general population regarding the impact of physical activity and other metabolic risk factors on QUICKI. Accordingly, comprehensive efforts which target these factors are needed to improve truckers' physical activity levels and other metabolic risks.

Beneficial metabolic role of ß-arrestin-1 expressed by AgRP neurons.

ß-Arrestin-1 and ß-arrestin-2 have emerged as important signaling molecules that modulate glucose fluxes in several peripheral tissues. The potential roles of neuronally expressed ß-arrestins in regulating glucose homeostasis remain unknown. We here report that mice lacking ß-arrestin-1 (barr1) selectively in AgRP neurons displayed impaired glucose tolerance and insulin sensitivity when consuming an obesogenic diet, while mice overexpressing barr1 selectively in AgRP neurons were protected against obesity-associated metabolic impairments. Additional physiological, biochemical, and electrophysiological data indicated that the presence of barr1 is essential for insulin-mediated hyperpolarization of AgRP neurons. As a result, barr1 expressed by AgRP neurons regulates efferent neuronal pathways that suppress hepatic glucose production and promote lipolysis in adipose tissue. Mice lacking ß-arrestin-2 (barr2) selectively in AgRP neurons showed no substantial metabolic phenotypes. Our data suggest that agents able to enhance the activity of barr1 in AgRP neurons may prove beneficial as antidiabetic drugs.

Brief, daily meditation enhances attention, memory, mood, and emotional regulation in non-experienced meditators.

Meditation is an ancient practice that cultivates a calm yet focused mind; however, little is known about how short, practical meditation practices affect cognitive functioning in meditation-naïve populations. To address this question, we randomized subjects (ages of 18-45) who were non-experienced meditators into either a 13-min daily guided meditation session or a 13-min daily podcast listening session (control group) for a total duration of 8 weeks. We examined the effects of the daily meditation practice relative to podcast listening on mood, prefrontal and hippocampal functioning, baseline cortisol levels, and emotional regulation using the Trier Social Stress Test (TSST). Compared to our control group, we found that 8 but not 4 weeks of brief, daily meditation decreased negative mood state and enhanced attention, working memory, and recognition memory as well as decreased state anxiety scores on the TSST. Furthermore, we report that meditation-induced changes in emotional regulation are more strongly linked to improved affective state than improved cognition. This study not only suggests a lower limit for the duration of brief daily meditation needed to see significant benefits in non-experienced meditators, but suggests that even relatively short daily meditation practice can have similar behavioral effects as longer duration and higher-intensity mediation practices.

Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis.

Adaptive thermogenesis is the process of heat generation in response to cold stimulation. It is under the control of the sympathetic nervous system, whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through ß3-adrenergic receptors to activate brown adipose tissue and by 'browning' white adipose tissue. Recent studies have reported that alternative activation of macrophages in response to interleukin (IL)-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and that this activation provides an alternative source of locally produced catecholamines during the thermogenic process. Here we report that the deletion of Th in hematopoietic cells of adult mice neither alters energy expenditure upon cold exposure nor reduces browning in inguinal adipose tissue. Bone marrow-derived macrophages did not release NE in response to stimulation with IL-4, and conditioned media from IL-4-stimulated macrophages failed to induce expression of thermogenic genes, such as uncoupling protein 1 (Ucp1), in adipocytes cultured with the conditioned media. Furthermore, chronic treatment with IL-4 failed to increase energy expenditure in wild-type, Ucp1-/- and interleukin-4 receptor-α double-negative (Il4ra-/-) mice. In agreement with these findings, adipose-tissue-resident macrophages did not express TH. Thus, we conclude that alternatively activated macrophages do not synthesize relevant amounts of catecholamines, and hence, are not likely to have a direct role in adipocyte metabolism or adaptive thermogenesis.

Work and Chronic Disease: Comparison of Cardiometabolic Risk Markers Between Truck Drivers and the General US Population.

OBJECTIVE: US long-haul truck drivers experience a wide array of excess cardiometabolic disease (CMD) risks unique to their occupation. How these risks translate to, and potentially induce, elevations in the clinical CMD risk profile of this population is unknown. METHODS: A non-experimental, descriptive, cross-sectional design was employed to collect anthropometric and biometric data from 115 long-haul truckers to generate for the first time a comprehensive CMD risk marker profile, which was then compared with the general US population. The relationships between CMD risk markers and CMD outcomes were examined for both populations. RESULTS: The long-haul trucker sample presented elevated CMD risk markers, generally scoring significantly worse than the general population. Associations between CMD risk markers and disease states varied between both populations. CONCLUSIONS: US long-haul truck drivers' distinctive CMD risk profile indicates occupationally-linked CMD pathogenesis.

The effects of improved metabolic risk factors on bone turnover markers after 12 weeks of simvastatin treatment with or without exercise.

OBJECTIVE: Emerging evidence supports an association between metabolic risk factors and bone turnover. Statins and exercise independently improve metabolic risk factors; however whether improvements in metabolic risk factor affects bone turnover is unknown. The purpose of the present study was to: 1) evaluate the relationship between metabolic risk factors and bone turnover; and 2) determine if improvements in metabolic risk factors after 12 weeks of statin treatment, exercise or the combination affect bone turnover. METHODS: Fifty participants with ≥2 metabolic syndrome defining characteristics were randomly assigned to one of three groups: statin (STAT: simvastatin, 40 mg/day), exercise (EX: brisk walking and/or slow jogging, 45 minutes/day, 5 days/week), or the combination (STAT+EX). Body composition and whole body bone mineral density were measured with dual energy X-ray absorptiometry. Serum markers of bone formation (bone specific alkaline phosphatase, BAP; osteocalcin, OC), resorption (C-terminal peptide of type I collagen, CTX) and metabolic risk factors were determined. Two-factor (time, group) repeated-measures ANCOVA was used to examine changes of metabolic risk factors and bone turnover. General linear models were used to determine the effect of pre-treatment metabolic risk factors on post-treatment bone turnover marker outcomes. RESULTS: Participants with ≥4 metabolic syndrome defining characteristics had lower pre-treatment OC than those with 3 or fewer. OC was negatively correlated with glucose, and CTX was positively correlated with cholesterol. STAT or STAT+EX lowered total and LDL cholesterol. The OC to CTX ratio decreased in all groups with no other significant changes in bone turnover. Higher pre-treatment insulin or body fat predicted a greater CTX reduction and a greater BAP/CTX increase. CONCLUSION: Metabolic risk factors were negatively associated with bone turnover markers. Short-term statin treatment with or without exercise lowered cholesterol and all treatments had a small effect on bone turnover.

One bout of exercise alters free-living postprandial glycemia in type 2 diabetes.

PURPOSE: Elevated postprandial glycemic (PPG) excursions are significant risk factors for cardiovascular disease in type 2 diabetes patients. In this study, we tested if and for how many meals a single bout of exercise would reduce PPG responses to subsequent meals in type 2 diabetes (T2D) patients using a continuous glucose monitor system (CGMS). METHODS: We recruited nine sedentary (<30 min·wk(-1) of exercise) individuals with T2D (mean ± SD; body mass index = 36.0 ± 1.1 kg·m(-2), age = 60.3 ± 1.0 yr, HbA1c = 6.3% ± 0.2%). The subjects consumed a eucaloric diet (51% carbohydrate, 31% fat, and 18% protein) consisting of three meals, identical in composition, for a 2-d period while wearing a continuous glucose monitor system in two different conditions (exercise [EX], one 60-min bout at 60%-75% of heart rate reserve performed before breakfast), vs a sedentary [SED] condition). We quantified 24-h average glucose, PPG area under the curve (AUC; 4-h glucose AUC after meals), and PPG-2 h (2 h postprandial glucose). RESULTS: EX significantly reduced average [glucose] during the first 24-h period (P = 0.03). EX caused a reduction in PPG-AUC (P = 0.02) for all of the meals during the 2 d (main effect between conditions). A comparison between the EX and the SED conditions at each meal revealed that EX reduced PPG-AUC after the second meal of day 1 (lunch) (P = 0.04). PPG-2 h was not significantly different between EX and SED. CONCLUSIONS: Although a single EX bout does lower 24-h average [glucose], it only significantly lowered PPG-AUC at the second meal after the bout, suggesting that daily exercise may be needed to most effectively improve PPG at the advent of exercise training in T2D patients.

Simvastatin impairs exercise training adaptations.

OBJECTIVES: This study sought to determine if simvastatin impairs exercise training adaptations. BACKGROUND: Statins are commonly prescribed in combination with therapeutic lifestyle changes, including exercise, to reduce cardiovascular disease risk in patients with metabolic syndrome. Statin use has been linked to skeletal muscle myopathy and impaired mitochondrial function, but it is unclear whether statin use alters adaptations to exercise training. METHODS: This study examined the effects of simvastatin on changes in cardiorespiratory fitness and skeletal muscle mitochondrial content in response to aerobic exercise training. Sedentary overweight or obese adults with at least 2 metabolic syndrome risk factors (defined according to National Cholesterol Education Panel Adult Treatment Panel III criteria) were randomized to 12 weeks of aerobic exercise training or to exercise in combination with simvastatin (40 mg/day). The primary outcomes were cardiorespiratory fitness and skeletal muscle (vastus lateralis) mitochondrial content (citrate synthase enzyme activity). RESULTS: Thirty-seven participants (exercise plus statins: n = 18; exercise only: n = 19) completed the study. Cardiorespiratory fitness increased by 10% (p < 0.05) in response to exercise training alone, but was blunted by the addition of simvastatin resulting in only a 1.5% increase (p < 0.005 for group by time interaction). Similarly, skeletal muscle citrate synthase activity increased by 13% in the exercise-only group (p < 0.05), but decreased by 4.5% in the simvastatin-plus-exercise group (p < 0.05 for group-by-time interaction). CONCLUSIONS: Simvastatin attenuates increases in cardiorespiratory fitness and skeletal muscle mitochondrial content when combined with exercise training in overweight or obese patients at risk of the metabolic syndrome. (Exercise, Statins, and the Metabolic Syndrome; NCT01700530).

Lowering physical activity impairs glycemic control in healthy volunteers.

INTRODUCTION: Postprandial glucose (PPG) is an independent predictor of cardiovascular events and death, regardless of diabetes status. Whereas changes in physical activity produce changes in insulin sensitivity, it is not clear whether changes in daily physical activity directly affect PPG in healthy free-living persons. METHODS: We used continuous glucose monitors to measure PPG and PPG excursions (ΔPPG, postmeal - premeal blood glucose) at 30-min increments after meals in healthy habitually active volunteers (n = 12, age = 29 ± 1 yr, body mass index = 23.6 ± 0.9 kg·m(-2), VO2max = 53.6 ± 3.0 mL·kg(-1)·min(-1)) during 3 d of habitual (≥10,000 steps per day) and reduced (<5000 steps per day) physical activity. Diets were standardized across monitoring periods, and fasting-state oral glucose tolerance tests (OGTT) were performed on the fourth day of each monitoring period. RESULTS: During 3 d of reduced physical activity (12,956 ± 769 to 4319 ± 256 steps per day), PPG increased at 30 and 60 min after a meal (6.31 ± 0.19 to 6.68 ± 0.23 mmol·L(-1) and 5.75 ± 0.16 to 6.26 ± 0.28 mmol·L(-1), P < 0.05 relative to corresponding active time point), and ΔPPG increased by 42%, 97%, and 33% at 30, 60, and 90 min after a meal, respectively (P < 0.05). Insulin and C-peptide responses to the OGTT increased after 3 d of reduced activity (P < 0.05), and the glucose response to the OGTT did not change significantly. CONCLUSIONS: Thus, despite evidence of compensatory increases in plasma insulin during an OGTT, ΔPPG assessed by continuous glucose monitoring systems increased markedly during 3 d of reduced physical activity in otherwise healthy free-living individuals. These data indicate that daily physical activity is an important mediator of glycemic control, even among healthy individuals, and reinforce the utility of physical activity in preventing pathologies associated with elevated PPG.

Seven days of aerobic exercise training improves conduit artery blood flow following glucose ingestion in patients with type 2 diabetes.

The vasodilatory effects of insulin account for up to 40% of insulin-mediated glucose disposal; however, insulin-stimulated vasodilation is impaired in individuals with type 2 diabetes, limiting perfusion and delivery of glucose and insulin to target tissues. To determine whether exercise training improves conduit artery blood flow following glucose ingestion, a stimulus for increasing circulating insulin, we assessed femoral blood flow (FBF; Doppler ultrasound) during an oral glucose tolerance test (OGTT; 75 g glucose) in 11 overweight or obese (body mass index, 34 ± 1 kg/m²), sedentary (peak oxygen consumption, 23 ± 1 ml·kg⁻¹·min⁻¹) individuals (53 ± 2 yr) with non-insulin-dependent type 2 diabetes (HbA1c, 6.63 ± 0.18%) before and after 7 days of supervised treadmill and cycling exercise (60 min/day, 60-75% heart rate reserve). Fasting glucose, insulin, and FBF were not significantly different after 7 days of exercise, nor were glucose or insulin responses to the OGTT. However, estimates of whole body insulin sensitivity (Matsuda insulin sensitivity index) increased (P < 0.05). Before exercise training, FBF did not change significantly during the OGTT (1 ± 7, -7 ± 5, 0 ± 6, and 0 ± 5% of fasting FBF at 75, 90, 105, and 120 min, respectively). In contrast, after exercise training, FBF increased by 33 ± 9, 39 ± 14, 34 ± 7, and 48 ± 18% above fasting levels at 75, 90, 105, and 120 min, respectively (P < 0.05 vs. corresponding preexercise time points). Additionally, postprandial glucose responses to a standardized breakfast meal consumed under "free-living" conditions decreased during the final 3 days of exercise (P < 0.05). In conclusion, 7 days of aerobic exercise training improves conduit artery blood flow during an OGTT in individuals with type 2 diabetes.