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Short sleep duration is prevalent in modern society and may be contributing to type 2 diabetes prevalence. This review will explore the effects of sleep restriction on glycemic control, the mechanisms causing insulin resistance, and whether exercise can offset changes in glycemic control. Chronic sleep restriction may also contribute to a decrease in physical activity leading to further health complications., (Copyright © 2024 by the American College of Sports Medicine.)

Impaired endothelial insulin signaling and consequent blunting of insulin-induced vasodilation is a feature of type 2 diabetes (T2D) that contributes to vascular disease and glycemic dysregulation. However, the molecular mechanisms underlying endothelial insulin resistance remain poorly known. Herein, we tested the hypothesis that endothelial insulin resistance in T2D is attributed to reduced expression of heat shock protein 72 (HSP72). HSP72 is a cytoprotective chaperone protein that can be upregulated with heating and is reported to promote insulin sensitivity in metabolically active tissues, in part via inhibition of JNK activity. Accordingly, we further hypothesized that, in individuals with T2D, 7 days of passive heat treatment via hot water immersion to waist level would improve leg blood flow responses to an oral glucose load (i.e., endogenous insulin stimulation) via induction of endothelial HSP72. In contrast, we found that: 1 ) endothelial insulin resistance in T2D mice and humans was not associated with reduced HSP72 in aortas and venous endothelial cells, respectively; 2 ) after passive heat treatment, improved leg blood flow responses to an oral glucose load did not parallel with increased endothelial HSP72; and 3 ) downregulation of HSP72 (via small-interfering RNA) or upregulation of HSP72 (via heating) in cultured endothelial cells did not impair or enhance insulin signaling, respectively, nor was JNK activity altered. Collectively, these findings do not support the hypothesis that reduced HSP72 is a key driver of endothelial insulin resistance in T2D but provide novel evidence that lower-body heating may be an effective strategy for improving leg blood flow responses to glucose ingestion-induced hyperinsulinemia.

Loss of ovarian hormones leads to increased adiposity and insulin resistance (IR), increasing the risk for cardiovascular and metabolic diseases. The purpose of this study was to investigate whether the molecular mechanism behind the adverse systemic and adipose tissue-specific metabolic effects of ovariectomy requires loss of signaling through estrogen receptor alpha (ERα) or estrogen receptor β (ERβ). We examined ovariectomized (OVX) and ovary-intactwild-type (WT), ERα-null (αKO), and ERβ-null (βKO) female mice (age ~49 weeks; n = 7-12/group). All mice were fed a phytoestrogen-free diet (<15 mg/kg) and either remained ovary-intact (INT) or were OVX and followed for 12 weeks. Body composition, energy expenditure, glucose tolerance, and adipose tissue gene and protein expression were analyzed. INT αKO were ~25% fatter with reduced energy expenditure compared to age-matched INT WT controls and βKO mice (all P < 0.001). Following OVX, αKO mice did not increase adiposity or experience a further increase in IR, unlike WT and βKO, suggesting that loss of signaling through ERα mediates OVX-induced metabolic dysfunction. In fact, OVX in αKO mice (i.e., signaling through ERβ in the absence of ERα) resulted in reduced adiposity, adipocyte size, and IR (P < 0.05 for all). βKO mice responded adversely to OVX in terms of increased adiposity and development of IR. Together, these findings challenge the paradigm that ERα mediates metabolic protection over ERβ in all settings. These findings lead us to suggest that, following ovarian hormone loss, ERβ may mediate protective metabolic benefits.

Females are typically more insulin sensitive than males, which may be partly attributed to greater brown adipose tissue (BAT) activity and uncoupling protein 1 (UCP1) content. Accordingly, we tested the hypothesis that UCP1 deletion would abolish sex differences in insulin sensitivity and that whitening of thoracic periaortic BAT caused by UCP1 loss would be accompanied with impaired thoracic aortic function. Furthermore, because UCP1 exerts antioxidant effects, we examined whether UCP1 deficiency-induced metabolic dysfunction was mediated by oxidative stress. Compared with males, female mice had lower HOMA- and AT-insulin resistance (IR) despite no significant differences in BAT UCP1 content. UCP1 ablation increased HOMA-IR, AT-IR, and whitening of BAT in both sexes. Expression of UCP1 in thoracic aorta was greater in wild-type females compared with males. Importantly, deletion of UCP1 enhanced aortic vasomotor function in females only. UCP1 ablation did not promote oxidative stress in interscapular BAT. Furthermore, daily administration of the free radical scavenger tempol for 8 wk did not abrogate UCP1 deficiency-induced increases in adiposity, hyperinsulinemia, or liver steatosis. Collectively, we report that 1 ) in normal chow-fed mice housed at 25°C, aortic UCP1 content was greater in females than males and its deletion improved ex vivo aortic vasomotor function in females only; 2 ) constitutive UCP1 content in BAT was similar between females and males and loss of UCP1 did not abolish sex differences in insulin sensitivity; and 3 ) the metabolic disruptions caused by UCP1 ablation did not appear to be contingent upon increased oxidative stress in mice under normal dietary conditions.

Introduction: In the absence of exercise training, rats selectively bred for high intrinsic aerobic capacity (high-capacity running (HCR)) are protected against ovariectomy (OVX)-induced insulin resistance (IR) and obesity compared with those bred for low intrinsic aerobic capacity (low-capacity running (LCR))., Purpose: This study determined whether OVX HCR rats remain protected with exposure to high-fat diet (HFD) compared with OVX LCR rats., Methods: Female HCR and LCR rats (n = 36; age, 27-33 wk) underwent OVX and were randomized to a standard chow diet (NC, 5% kcal fat) or HFD (45% kcal fat) ad libitum for 11 wk. Total energy expenditure, resting energy expenditure, spontaneous physical activity (SPA), and glucose tolerance were assessed midway, whereas fasting circulating metabolic markers, body composition, adipose tissue distribution, and skeletal muscle adenosine monophosphate-activated protein kinase (AMPK), and mitochondrial markers were assessed at sacrifice., Results: Both HCR and LCR rats experienced HFD-induced increases in total and visceral adiposity after OVX. Despite similar gains in adiposity, HCR rats were protected from HFD-induced IR and reduced total energy expenditure observed in LCR rats (P < 0.05). This metabolic protection was likely attributed to a compensatory increase in SPA and associated preservation of skeletal muscle AMPK activity in HCR; however, HFD significantly reduced SPA and AMPK activity in LCR (P < 0.05). In both lines, HFD reduced citrate synthase activity, gene expression of markers of mitochondrial biogenesis (tFAM, NRF1, and PGC-1α), and protein levels of mitochondrial oxidative phosphorylation complexes I, II, IV, and V in skeletal muscle (all P < 0.05)., Conclusion: After OVX, HCR and LCR rats differentially respond to HFD such that HCR increase while LCR decrease SPA. This "physical activity compensation" likely confers protection from HFD-induced IR and reduced energy expenditure in HCR rats.

High-capacity running (HCR) rats are protected against the early (i.e., ∼ 11 wk postsurgery) development of ovariectomy (OVX)-induced insulin resistance (IR) compared with low-capacity running (LCR) rats. The purpose of this study was to utilize the hyperinsulinemic euglycemic clamp to determine whether 1) HCR rats remain protected from OVX-induced IR when the time following OVX is extended to 27 wk and 2) tissue-specific glucose uptake differences are responsible for the protection in HCR rats under sedentary conditions. Female HCR and LCR rats (n = 40; aged ∼ 22 wk) randomly received either OVX or sham (SHM) surgeries and then underwent the clamp 27 wk following surgeries. [3-(3)H]glucose was used to determine glucose clearance, whereas 2-[(14)C]deoxyglucose (2-DG) was used to assess glucose uptake in skeletal muscle, brown adipose tissue (BAT), subcutaneous white adipose tissue (WAT), and visceral WAT. OVX decreased the glucose infusion rate and glucose clearance in both lines, but HCR had better insulin sensitivity than LCR (P < 0.05). In both lines, OVX significantly reduced glucose uptake in soleus and gastrocnemius muscles; however, HCR showed ∼ 40% greater gastrocnemius glucose uptake compared with LCR (P < 0.05). HCR also exhibited greater glucose uptake in BAT and visceral WAT compared with LCR (P < 0.05), yet these tissues were not affected by OVX in either line. In conclusion, OVX impairs insulin sensitivity in both HCR and LCR rats, likely driven by impairments in insulin-mediated skeletal muscle glucose uptake. HCR rats have greater skeletal muscle, BAT, and WAT insulin-mediated glucose uptake, which may aid in protection against OVX-associated insulin resistance.

Aims: Serum chemerin concentrations are elevated in obese individuals and may play a role in type 2 diabetes. Exercise improves insulin sensitivity, which may be related to changes in chemerin. This study explored how an acute bout of aerobic exercise affected chemerin levels in non-diabetic obese adults., Methods: Blood samples from 11 obese adults were obtained during two separate conditions: sedentary (SED) and exercise (EX; 60-65% VO2peak). Samples were drawn at baseline, immediately following exercise and hourly for an additional 2h. ANOVA was used to test for differences in chemerin between conditions., Results: Unadjusted analysis showed no difference in overall change (baseline to 2h post) in chemerin between conditions. During the 2-h post-exercise period, chemerin decreased to 12% below baseline, compared to a 2.5% increase above baseline during that time period on the sedentary day (p=0.06, difference in post-to-2h change between conditions). Controlling for homeostatic model assessment of insulin resistance (HOMA-IR), a significant difference existed between EX and SED in the change in chemerin from baseline to 2-h post (p=0.02). Stratified analyses showed a consistent exercise-induced decrease in chemerin among non-insulin resistant subjects, while chemerin increased during exercise among insulin resistant subjects, and then decreased post-exercise., Conclusion: An acute bout of exercise in obese individuals may elicit a drop in chemerin levels during the post-exercise period, and this response may vary based on insulin resistance., (Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background: Adolescents consume more sugar-sweetened beverages than do individuals in any other age group, but it is unknown how the type of sugar-sweetened beverage affects metabolic health in this population., Objective: The objective was to compare the metabolic health effects of short-term (2-wk) consumption of high-fructose (HF) and high-glucose (HG)-sweetened beverages in adolescents (15-20 y of age)., Design: In a counterbalanced, single-blind fashion, 40 male and female adolescents completed two 2-wk trials that included 1) an HF trial in which they consumed 710 mL of a sugar-sweetened beverage/d (equivalent to 50 g fructose/d and 15 g glucose/d) for 2 wk and 2) an HG trial in which they consumed 710 mL of a sugar-sweetened beverage/d (equivalent to 50 g glucose/d and 15 g fructose/d) for 2 wk in addition to their normal ad libitum diet. In addition, the participants maintained similar physical activity levels during each trial. The day after each trial, insulin sensitivity and resistance [assessed via Quantitative Insulin Sensitivity Check Index (QUICKI) and homeostatic model assessment of insulin resistance (HOMA-IR) index] and fasting and postprandial glucose, lactate, lipid, cholesterol, insulin, C-peptide, insulin secretion, and clearance responses to HF or HG mixed meals were assessed., Results: Body weight, QUICKI (whole-body insulin sensitivity), HOMA-IR (hepatic insulin resistance), and fasting lipids, cholesterol, glucose, lactate, and insulin secretion or clearance were not different between trials. Fasting HDL- and HDL₃-cholesterol concentrations were ∼10-31% greater (P < 0.05) in female adolescents than in male adolescents. Postprandial triacylglycerol, HDL-cholesterol, HDL₃-cholesterol, and glucose concentrations were not different between HF and HG trials. The lactate incremental area under the curve was ∼3.7-fold greater during the HF trial (P < 0.05), whereas insulin secretion was 19% greater during the HG trial (P < 0.05)., Conclusions: Moderate amounts of HF- or HG-sweetened beverages for 2 wk did not have differential effects on fasting or postprandial cholesterol, triacylglycerol, glucose, or hepatic insulin clearance in weight-stable, physically active adolescents., (© 2014 American Society for Nutrition.)

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.

Supplemental digital content is available in the text. Despite the acknowledgment of exercise as a cornerstone in the management of type 2 diabetes (T2D), the importance of exercise timing has only recently been considered. Purpose: This study sought to determine the effect of diurnal exercise timing on glycemic control in individuals enrolled in a 12-wk supervised multimodal exercise training program. A secondary aim was to determine the effect of diurnal exercise timing on the circadian rhythm of wrist skin temperature. Methods: Forty sedentary, overweight adults (mean ± SD, age = 51 ± 13 yr; body mass index = 30.9 ± 4.2 kg·m−2; women, n = 23) with and without (n = 20) T2D diagnosis were randomly allocated to either a morning (amEX) or an evening (pmEX) exercise training group. The supervised 12-wk (3 d·wk−1) program, comprised 30 min of moderate-intensity walking and 4 resistance-based exercises (3 sets, 12–18 repetitions each). Glycemic outcomes (glycated hemoglobin, fasting glucose, postprandial glucose) and wrist skin temperature were assessed at baseline and postintervention. Results: Exercise training improved (main effect of time, all P < 0.01) all glycemic outcomes; however, this was independent of allocation to either the amEX (Hedge's g , 0.23–0.90) or the pmEX (Hedge's g , 0.16–0.90) group. Accordingly, the adopted exercise training program did not alter the circadian rhythm of skin temperature. When only T2D individuals were compared, amEX demonstrated greater effects (all Hedge's g) on glycated hemoglobin (amEX, 0.57; pmEX, 0.32), fasting glucose (amEX, 0.91; pmEX, 0.53), and postprandial glucose (amEX, 1.12; pmEX, 0.71) but was not statistically different. Conclusions: Twelve weeks of multimodal exercise training improved glycemic control and postprandial glycemic responses in overweight non-T2D and T2D individuals. However, no distinct glycemic benefits or alterations in circadian rhythm were associated with morning versus evening exercise, when performed three times per week in this cohort. [ABSTRACT FROM AUTHOR]

The role of estrogen receptor-α (ERα) signaling in immunometabolic function is established in females. However, its necessity in males, while appreciated, requires further study. Accordingly, we first determined whether lower metabolic function in male mice compared with females is related to reduced ERα expression. ERα protein expression in metabolically active tissues was lower in males than in females, and this lower expression was associated with worse glucose tolerance. Second, we determined whether ERα is required for optimal immunometabolic function in male mice consuming a chow diet. Despite lower expression of ERα in males, its genetic ablation (KO) caused an insulin-resistant phenotype characterized by enhanced adiposity, glucose intolerance, hepatic steatosis, and metaflammation in adipose tissue and liver. Last, we determined whether ERα is essential for exercise-induced metabolic adaptations. Twelve-week-old wild-type (WT) and ERα KO mice either remained sedentary (SED) or were given access to running wheels (WR) for 10 wk while fed an obesogenic diet. Body weight and fat mass were lower in WR mice regardless of genotype. Daily exercise obliterated immune cell infiltration and inflammatory gene transcripts in adipose tissue in both genotypes. In the liver, however, wheel running suppressed hepatic steatosis and inflammatory gene transcripts in WT but not in KO mice. In conclusion, the present findings indicate that ERα is required for optimal immunometabolic function in male mice despite their reduced ERα protein expression in metabolically active tissues. Furthermore, for the first time, we show that ERα signaling appears to be obligatory for exercise-induced prevention of hepatic steatosis. [ABSTRACT FROM AUTHOR]

Loss of ovarian hormones is associated with increased adiposity, white adipose tissue (WAT) inflammation, and insulin resistance (IR). Previous work demonstrated ovariectomized (OVX) rats bred for high aerobic fitness (HCR) are protected against weight gain and IR compared to rats bred for low aerobic fitness (LCR) yet wheel running prevents OVX-induced IR in LCR rats. The purpose of this study was to determine whether adipose tissue immunometabolic characteristics from female HCR and LCR rats differs before or after OVX, and whether wheel running mitigates OVX-induced adipose tissue immunometabolic changes in LCR rats. Female OVX HCR and LCR rats were all fed a high fat diet (HFD) (n = 7-8/group) and randomized to either a running wheel or remain sedentary for 11 weeks. Ovary-intact rats (n = 7-12/group) were fed a standard chow diet with no wheel. Ovary-intact LCR rats had a greater visceral WAT inflammatory profile compared to HCR. Following OVX, sedentary LCR rats had greater serum leptin (p<0.001) and WAT inflammation (p<0.05) than sedentary HCR. Wheel running normalized the elevated serum leptin and reduced both visceral (p<0.05) and subcutaneous (p<0.03) WAT inflammatory markers in the LCR rats. Paradoxically, wheel running increased some markers of WAT inflammation in OVX HCR rats (p<0.05), which correlated with observed weight gain. Taken together, HCR rats appear to have a healthier WAT immune and metabolic profile compared to LCR, even following OVX. Wheel running improves WAT health in previously sedentary LCR rats. On the other hand, increased WAT inflammation is associated with adiposity gain despite a high volume of wheel running in HCR rats. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that female mice null for uncoupling protein 1 (UCP1) would have increased susceptibility to Western diet-induced "whitening" of brown adipose tissue (AT) and glucose intolerance. Six-week-old C57BL/6J wild-type (WT) and UCP1 knockout (UCP1-/-) mice, housed at 25°C, were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 28 wk. Loss of UCP1 had no effect on energy intake, energy expenditure, spontaneous physical activity, weight gain, or visceral white AT mass. Despite similar susceptibility to weight gain compared with WT, UCP1-/- exhibited whitening of brown AT evidenced by a striking ~500% increase in mass and appearance of large unilocular adipocytes, increased expression of genes related to inflammation, immune cell infiltration, and endoplasmic reticulum/oxidative stress (P < 0.05), and decreased mitochondrial subunit protein (COX I, II, III, and IV, P < 0.05), all of which were exacerbated by Western diet (P < 0.05). UCP1-/- mice also developed liver steatosis and glucose intolerance, which was worsened by Western diet. Collectively, these findings demonstrate that loss of UCP1 exacerbates Western diet-induced whitening of brown AT, glucose intolerance, and induces liver steatosis. Notably, the adverse metabolic manifestations of UCP1-/- were independent of changes in body weight, visceral adiposity, and energy expenditure. These novel findings uncover a previously unrecognized metabolic protective role of UCP1 that is independent of its already established role in energy homeostasis. [ABSTRACT FROM AUTHOR]

Introduction: In the absence of exercise training, rats selectively bred for high intrinsic aerobic capacity (high-capacity running (HCR)) are protected against ovariectomy (OVX)-induced insulin resistance (IR) and obesity compared with those bred for low intrinsic aerobic capacity (low-capacity running (LCR)). Purpose: This study determined whether OVX HCR rats remain protected with exposure to high-fat diet (HFD) compared with OVX LCR rats. Methods: Female HCR and LCR rats (n = 36; age, 27-33 wk) underwent OVX and were randomized to a standard chow diet (NC, 5% kcal fat) or HFD (45% kcal fat) ad libitum for 11 wk. Total energy expenditure, resting energy expenditure, spontaneous physical activity (SPA), and glucose tolerance were assessed midway, whereas fasting circulating metabolic markers, body composition, adipose tissue distribution, and skeletal muscle adenosine monophosphate-activated protein kinase (AMPK), and mitochondrial markers were assessed at sacrifice. Results: Both HCR and LCR rats experienced HFD-induced increases in total and visceral adiposity after OVX. Despite similar gains in adiposity, HCR rats were protected from HFD-induced IR and reduced total energy expenditure observed in LCR rats (P < 0.05). This metabolic protection was likely attributed to a compensatory increase in SPA and associated preservation of skeletal muscle AMPK activity in HCR; however, HFD significantly reduced SPA and AMPK activity in LCR (P < 0.05). In both lines, HFD reduced citrate synthase activity, gene expression of markers of mitochondrial biogenesis (tFAM, NRF1, and PGC-1α), and protein levels of mitochondrial oxidative phosphorylation complexes I, II, IV, and V in skeletal muscle (all P < 0.05). Conclusion: After OVX, HCR and LCR rats differentially respond to HFD such that HCR increase while LCR decrease SPA. This ''physical activity compensation'' likely confers protection from HFD-induced IR and reduced energy expenditure in HCR rats. [ABSTRACT FROM AUTHOR]

A frequent eating pattern may alter glycaemic control and augment postprandial insulin concentrations in some individuals due to the truncation of the previous postprandial period by a subsequent meal. The present study examined glucose, insulin, C-peptide and glucose-dependent insulinotropic peptide (GIP) responses in obese individuals when meals were ingested in a high-frequency pattern (every 2 h, 6M) or in a low-frequency pattern (every 4 h, 3M) over 12 h. It also examined these postprandial responses to high-frequency, high-protein meals (6MHP). In total, thirteen obese subjects completed three 12 h study days during which they consumed 6276 kJ (1500 kcal): (1) 3M – 15 % protein and 65 % carbohydrate; (2) 6M – 15 % protein and 65 % carbohydrate; (3) 6MHP – 45 % protein and 35 % carbohydrate. Blood samples were collected every 10 min and analysed for glucose, insulin, C-peptide and GIP. Insulin total AUC (tAUC) and peak insulin concentrations (P< 0·05) were higher in the 3M condition than in the 6M condition, but there were no differences in glucose tAUC between the conditions. The 6MHP regimen (glucose: 3569 (se 83) mmol/l × min (64·3 (se 1·5) g/dl × min), insulin: 1·577 (se 0·146) pmol/l (22·7 (se 2·1) μIU/dl) for 12 h) lowered glucose and insulin excursions more so over 12 h than either the 3M regimen (glucose: 3913 (se 78) mmol/l × min (70·5 (se 1·4) g/dl × min), insulin: 2·195 (se 0·146) pmol/l × min (31·6 (se 2·1) μIU/dl × min) for 12 h) or the 6M regimen (glucose: 3902 (se 83) mmol/l × min (70·3 (se 1·5) g/dl × min), insulin: 1·861 (se 0·174) pmol/l × min (26·8 (se 2·5) μIU/dl × min) for 12 h; P< 0·01). Insulin secretion, GIP concentrations and the glucose:insulin ratio were not altered by meal frequency or composition. In obese subjects, ingestion of meals in a low-frequency pattern does not alter glucose tAUC, but increases postprandial insulin responses. The substitution of carbohydrates with protein in a frequent meal pattern results in tighter glycaemic control and reduced postprandial insulin responses. [ABSTRACT FROM PUBLISHER]

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We hypothesized that insulin alters plasma free fatty acid (FFA) trafficking into intramyocellular (im) long-chain acylcarnitines (imLCAC) and triglycerides (imTG). Overnight-fasted adults (n = 41) received intravenous infusions of [U-13C]palmitate (0400-0900 h) and [U-13C]oleate (0800-1400 h) to label imTG and imLCAC. A euglycemic-hyperinsulinemic (1.0 mU·kg fat-free mass-1·min-1) clamp(0800-1400 h) and two muscle biopsies (0900 h, 1400 h) were performed. The patterns of [U-13C]palmitate incorporation into imTG-palmitate and palmitoylcarnitine were similar to those we reported in overnight postabsorptive adults (saline control); the intramyocellular palmitoylcarnitine enrichment was not different from and correlated with imTG-palmitate enrichment for both the morning (r = 0.38, P = 0.02) and afternoon (r = 0.44, P = 0.006) biopsy samples. Plasma FFA concentrations, flux, and the incorporation of plasma oleate into imTG-oleate during hyperinsulinemia were ~1/10th of that observed in the previous saline control studies (P < 0.001). At the time of the second biopsy, the enrichment in oleoylcarnitine was <25% of that in imTG-oleate and was not correlated with imTG-oleate enrichment. The intramyocellular nonesterified fatty acid-palmitate-to-imTGpalmitate enrichment ratio was greater (P < 0.05) in women than men, suggesting that sex differences in intramyocellular palmitate trafficking may occur under hyperinsulinemic conditions. We conclude that plasma FFA trafficking into imTG during hyperinsulinemia is markedly suppressed, and these newly incorporated FFA fatty acids do not readily enter the LCAC preoxidative pools. Hyperinsulinemia does not seem to inhibit the entry of fatty acids from imTG pools that were labeled under fasting conditions, possibly reflecting the presence of two distinct imTG pools that are differentially regulated by insulin. [ABSTRACT FROM AUTHOR]

Introduction: Ovariectomy and high-fat diet (HFD) worsen obesity and metabolic dysfunction associated with low aerobic fitness. Exercise training mitigates metabolic abnormalities induced by low aerobic fitness, but whether the protective effect is maintained after ovariectomy and HFD is unknown. Purpose: This study determined whether, after ovariectomy and HFD, exercise training improves metabolic function in rats bred for low intrinsic aerobic capacity. Methods: Female rats selectively bred for low (LCR) and high (HCR) intrinsic aerobic capacity (n = 30) were ovariectomized, fed HFD, and randomized to either a sedentary (SED) or voluntary wheel running (EX) group. Resting energy expenditure, glucose tolerance, and spontaneous physical activity were determined midway through the experiment, whereas body weight, wheel running volume, and food intake were assessed throughout the study. Body composition, circulating metabolic markers, and skeletal muscle gene and protein expression were measured at sacrifice. Results: EX reduced body weight and adiposity in LCR rats (-10% and -50%, respectively; P < 0.05) and, unexpectedly, increased these variables in HCR rats (+7% and +37%, respectively; P < 0.05) compared with their respective SED controls, likely because of dietary overcompensation. Wheel running volume was approximately fivefold greater in HCR than LCR rats, yet EX enhanced insulin sensitivity equally in LCR and HCR rats (P < 0.05). This EX-mediated improvement in metabolic function was associated with thee gene upregulation of skeletal muscle interleukin-6 and interleukin-10. EX also increased resting energy expenditure, skeletal muscle mitochondrial content (oxidative phosphorylation complexes and citrate synthase activity), and adenosine monophosphate-activated protein kinase activation similarly in both lines (all P <0.05). Conclusion: Despite a fivefold difference in running volume between rat lines, EX similarly improved systemic insulin sensitivity, resting energy expenditure, and skeletal muscle mitochondrial content and adenosine monophosphate-activated protein kinase activation in ovariectomized LCR and HCR rats fed HFD compared with their respective SED controls. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Purpose: Physical inactivity is associated with disruptions in glucose metabolism and energy balance, whereas energy restriction may blunt these adverse manifestations. During hypocaloric feeding, higher-protein intake maintains lean mass which is an important component of metabolic health. This study determined whether mild energy restriction preserves glycemic control during physical inactivity and whether this preservation is more effectively achieved with a higher-protein diet. Methods: Ten adults (24 ± 1 yr) consumed a control (64% carbohydrate, 20% fat, 16% protein) and higher-protein diet (50% carbohydrate, 20% fat, 30% protein) during two 10-d inactivity periods (>10,000 → ~5000 steps per day) in a randomized crossover design. Energy intake was decreased by ~400 kcal·d−1 to account for reduced energy expenditure associated with inactivity. A subset of subjects (n = 5) completed 10 d of inactivity while consuming 35% excess of their basal energy requirements, which served as a positive control condition (overfeeding+inactivity). Results: Daily steps were decreased from 12,154 ± 308 to 4275 ± 269 steps per day (P < 0.05) which was accompanied by reduced V˙O2max (−1.8 ± 0.7 mL·kg−1·min−1, P < 0.05), independent of diet conditions. No disruptions in fasting or postprandial glucose, insulin, and nonesterified fatty acids in response to 75 g of oral glucose were observed after inactivity for both diet conditions (P > 0.05). Overfeeding+inactivity increased body weight, body fat, homeostasis model assessment of insulin resistance, and 2-h postprandial glucose and insulin concentrations (P < 0.05), despite no changes in lipid concentrations. Conclusions: We show that independent of diet (normal vs higher-protein), mild energy restriction preserves metabolic function during short-term inactivity in healthy subjects. That is, metabolic deterioration with inactivity only manifests in the setting of energy surplus. [ABSTRACT FROM AUTHOR]