Attenuation of high-fat diet-induced weight gain by apolipoprotein A4.

Objective: Apolipoprotein A4 (APOA4) is synthesized by the small intestine in response to dietary lipids. Chronic exposure to a high-fat diet (HFD) desensitizes lipid-induced APOA4 production and attenuates brown adipose tissue (BAT) thermogenesis. We hypothesized that exogenous APOA4 could increase BAT thermogenesis and energy expenditure in HFD-fed mice, resulting in decreased obesity and improved glucose tolerance.

Sex-specific increases in myostatin and SMAD3 contribute to obesity-related insulin resistance in human skeletal muscle and primary human myotubes.

The purpose of the present study was to determine the effects of obesity and biological sex on myostatin expression in humans and to examine the direct effects of myostatin, SMAD2, and SMAD3 on insulin signaling in primary human skeletal muscle cells (HSkMCs). For , 15 lean [body mass index (BMI): 22.1 ± 0.

Apolipoprotein A4 Elevates Sympathetic Activity and Thermogenesis in Male Mice.

Long-chain fatty acids induce apolipoprotein A4 (APOA4) production in the small intestine and activate brown adipose tissue (BAT) thermogenesis. The increase in BAT thermogenesis enhances triglyceride clearance and insulin sensitivity. Acute administration of recombinant APOA4 protein elevates BAT thermogenesis in chow-fed mice.

Lactate-induced lactylation in skeletal muscle is associated with insulin resistance in humans.

Elevated circulating lactate has been associated with obesity and insulin resistance. The aim of the current study was to determine if lactate-induced lysine lactylation (kla), a post-translational modification, was present in human skeletal muscle and related to insulin resistance. Fifteen lean (Body Mass Index: 22.

Perspective: Pragmatic Exercise Recommendations for Older Adults: The Case for Emphasizing Resistance Training.

Optimal health benefits from exercise are achieved by meeting both aerobic and muscle strengthening guidelines, however, most older adults (OAs) do not exercise and the majority of those who do only perform one type of exercise. A pragmatic solution to this problem may be emphasizing a single exercise strategy that maximizes health benefits. The loss of muscle mass and strength at an accelerated rate are hallmarks of aging that, without intervention, eventually lead to physical disability and loss of independence.

Impact of Endurance and Resistance Training on Skeletal Muscle Glucose Metabolism in Older Adults.

Aging is associated with insulin resistance and the development of type 2 diabetes. While this process is multifaceted, age-related changes to skeletal muscle are expected to contribute to impaired glucose metabolism. Some of these changes include sarcopenia, impaired insulin signaling, and imbalances in glucose utilization.

Aerobic and resistance exercise training reverses age-dependent decline in NAD salvage capacity in human skeletal muscle.

Aging decreases skeletal muscle mass and strength, but aerobic and resistance exercise training maintains skeletal muscle function. NAD is a coenzyme for ATP production and a required substrate for enzymes regulating cellular homeostasis. In skeletal muscle, NAD is mainly generated by the NAD salvage pathway in which nicotinamide phosphoribosyltransferase (NAMPT) is rate-limiting.

Paternal high-fat diet enhances offspring whole-body insulin sensitivity and skeletal muscle insulin signaling early in life.

Evidence suggests that paternal diet can predispose offspring to metabolic dysfunction. Despite this knowledge, little is known regarding the effects of paternal high-fat feeding on offspring insulin sensitivity. The purpose of this study was to investigate for the first time the effects of paternal high-fat feeding on whole-body and skeletal muscle insulin action in young and adult offspring.

Blocking Wnt5a signaling decreases CD36 expression and foam cell formation in atherosclerosis.

Background And Aims: Wnt5a is a highly studied member of the Wnt family and recently has been implicated in the pathogenesis of atherosclerosis, but its precise role is unknown. Foam cell development is a critical process to atherosclerotic plaque formation. In the present study, we investigated the role of noncanonical Wnt5a signaling in the development of foam cells.

Sex-dependent reductions in high molecular weight adiponectin during acute hyperinsulinemia are prevented with endurance training in older females.

Objective: The high molecular weight (HMW) adiponectin isoform is considered the active form of adiponectin and is linked to insulin sensitivity and the reduced risk of developing cardiovascular disease. The purpose of the first study was to determine the effects of age and sex on the plasma HMW adiponectin response to acute hyperinsulinemia, and secondly determine whether either endurance or resistance exercise training could affect this response.

Design And Participants: Twenty-six healthy males (19-84 years) and twenty-six healthy females (18-76 years) were recruited and matched for BMI to examine the effects of sex and age on the plasma adiponectin response to a 2-hour hyperinsulinemic-euglycemic clamp.

Mice overexpressing growth hormone exhibit increased skeletal muscle myostatin and MuRF1 with attenuation of muscle mass.

Background: In contrast to the acute effects of growth hormone (GH) on skeletal muscle protein synthesis, long-term GH treatment appears to have negligible effects on muscle mass. Despite this knowledge, little is known regarding the chronic effects of GH on skeletal muscle protein synthesis and atrophy signaling pathways. The purpose of this study was to determine if protein synthesis pathways are attenuated and/or muscle atrophy intracellular signaling pathways are altered in the skeletal muscle of transgenic bovine GH (bGH) mice.

Plasma acylcarnitines during insulin stimulation in humans are reflective of age-related metabolic dysfunction.

The purpose of this study was to determine if plasma acylcarnitine (AC) profiling is altered under hyperinsulinemic conditions as part of the aging process. Fifteen young, lean (19-29 years) and fifteen middle-to older-aged (57-82 years) individuals underwent a 2-hr euglycemic-hyperinsulinemic clamp. Plasma samples were obtained at baseline, 20 min, 50 min, and 120 min for analysis of AC species and amino acids.

Age-related impairments in skeletal muscle PDH phosphorylation and plasma lactate are indicative of metabolic inflexibility and the effects of exercise training.

The purpose of this study was to determine whether plasma lactate and skeletal muscle glucose regulatory pathways, specifically PDH dephosphorylation, are impaired during hyperinsulinemic conditions in middle- to older-aged individuals and determine whether exercise training could improve key variables responsible for skeletal muscle PDH regulation. Eighteen young (19-29 yr; n = 9 males and 9 females) and 20 middle- to older-aged (57-82 yr; n = 10 males and 10 females) individuals underwent a 2-h euglycemic hyperinsulinemic clamp. Plasma samples were obtained at baseline and at 30, 50, 90, and 120 min for analysis of lactate, and skeletal muscle biopsies were performed at 60 min for analysis of protein associated with glucose metabolism.

Impairments in site-specific AS160 phosphorylation and effects of exercise training.

The purpose of this study was to determine if site-specific phosphorylation at the level of Akt substrate of 160 kDa (AS160) is altered in skeletal muscle from sedentary humans across a wide range of the adult life span (18-84 years of age) and if endurance- and/or strength-oriented exercise training could rescue decrements in insulin action and skeletal muscle AS160 phosphorylation. A euglycemic-hyperinsulinemic clamp and skeletal muscle biopsies were performed in 73 individuals encompassing a wide age range (18-84 years of age), and insulin-stimulated AS160 phosphorylation was determined. Decrements in whole-body insulin action were associated with impairments in insulin-induced phosphorylation of skeletal muscle AS160 on sites Ser-588, Thr-642, Ser-666, and phospho-Akt substrate, but not Ser-318 or Ser-751.

Lipid partitioning, incomplete fatty acid oxidation, and insulin signal transduction in primary human muscle cells: effects of severe obesity, fatty acid incubation, and fatty acid translocase/CD36 overexpression.

Context: Intracellular lipid partitioning toward storage and the incomplete oxidation of fatty acids (FA) have been linked to insulin resistance.

Objective: To gain insight into how intracellular lipid metabolism is related to insulin signal transduction, we examined the effects of severe obesity, excess FA, and overexpression of the FA transporter, FA translocase (FAT)/CD36, in primary human skeletal myocytes.

Design, Setting, And Patients: Insulin signal transduction, FA oxidation, and metabolism were measured in skeletal muscle cells harvested from lean and severely obese women.

Peroxisome proliferator-activated receptor-gamma coactivator-1alpha overexpression increases lipid oxidation in myocytes from extremely obese individuals.

Objective: To determine whether the obesity-related decrement in fatty acid oxidation (FAO) in primary human skeletal muscle cells (HSkMC) is linked with lower mitochondrial content and whether this deficit could be corrected via overexpression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha).

Research Design And Methods: FAO was studied in HSkMC from lean (BMI 22.4 +/- 0.

Substrate utilization during and after exercise in mild cystic fibrosis.

Purpose: To determine substrate utilization and energy expenditure during maximal and submaximal exercise and recovery in adolescents with cystic fibrosis (CF) and healthy age-matched controls (C).

Methods: Ten clinically stable CF patients (four girls, six boys; age = 10-22 yr) were matched by body mass index, age, gender, and Tanner stage to healthy controls. Subjects completed VO(2peak) testing and submaximal exercise (20 min) on a cycle ergometer at a relative intensity of 50% VO2(peak) and at an absolute power output (PO).

Intramuscular lipid metabolism, insulin action, and obesity.

With the increasing prevalence of obesity, research has focused on the molecular mechanism(s) linking obesity and skeletal muscle insulin resistance. Metabolic alterations within muscle, such as changes in the cellular location of fatty acid transporter proteins, decreased mitochondrial enzyme activity, and defects in mitochondrial morphology, likely contribute to obesity and insulin resistance. These defects are thought to play a role in the reduced skeletal muscle fatty acid oxidation and increased intramuscular lipid (IMCL) accumulation that is apparent with obesity and other insulin-resistant states such as type 2 diabetes.

Phosphorylation of the JAK2-STAT5 pathway in response to acute aerobic exercise.

Unlabelled: Growth hormone (GH) is a powerful stimulator of the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) pathway. Acute exercise is a known stimulus for GH secretion.

Purpose: The purpose of this study was to determine the phosphorylation of the JAK2-STAT5 pathway in human skeletal muscle in response to acute aerobic exercise.

The effect of exercise type on immunofunctional and traditional growth hormone.

The purpose of this study was to compare the growth hormone (GH) response, including the immunfunctional (IF) GH response, between an acute bout of aerobic and resistance exercise in the same subjects. Ten cross-trained males (24.3 +/- 1.

The impact of sex and exercise duration on growth hormone secretion.

Previous research clearly indicates a linear relationship between exercise intensity and growth hormone (GH) release and that this relationship is influenced by sex. The present study examined the GH response to increasing exercise duration in young men and women. Fifteen healthy subjects (8 men and 7 women) completed three randomly assigned exercise sessions (30, 60, and 120 min) at 70% of peak oxygen consumption.

Effects of acute aerobic and anaerobic exercise on blood markers of oxidative stress.

The purpose of this study was to compare oxidative modification of blood proteins, lipids, DNA, and glutathione in the 24 hours following aerobic and anaerobic exercise using similar muscle groups. Ten cross-trained men (24.3 +/- 3.

Hormonal responses to endurance and resistance exercise in females aged 19-69 years.

Thirty cross-trained, female subjects (19-69 years) completed an endurance exercise session (ES), a resistance exercise session (RS), and a control session (CS) in a randomized, balanced design. The ES consisted of 40 minutes of cycling at 75% maximum heart rate, and the RS consisted of 3 sets of 10 repetitions of eight exercises. During the CS, subjects performed no exercise.

Endogenous anabolic hormone responses to endurance versus resistance exercise and training in women.

Research in exercise endocrinology has flourished over the past few decades. In general, research examining short- and long-term hormone responses to endurance exercise preceded studies on resistance exercise, and research on women lagged behind research on men. Sufficient data are now available to allow a comparison of endogenous anabolic hormone responses to endurance versus resistance exercise and training in women.