The Human Plasma Proteome History, Character, and Diagnostic Prospects

Methods for assessment, e.g., anthropometric indicators and imaging techniques, of several phenotypes of human obesity, with special reference to abdominal fat content, have been evaluated. The correlation of fat distribution with age, gender, total body fat, energy balance, adipose tissue lipoprotein lipase and lipolytic activity, adipose tissue receptors, and genetic characteristics are discussed. Several secreted or expressed factors in the adipocyte are evaluated in the context of fat tissue localization. The body fat distribution and the metabolic profile in nonobese and obese individuals is discussed relative to lipolysis, antilypolysis and lipogenesis, insulin sensitivity, and glucose, lipid, and protein metabolism. Finally, the endocrine regulation of abdominal visceral fat in comparison with the adipose tissue localized in other areas is presented.

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Subcutaneous and visceral adipose tissue : Their relation to the metabolic syndrome

Excess intra-abdominal adipose tissue accumulation, often termed visceral obesity, is part of a phenotype including dysfunctional subcutaneous adipose tissue expansion and ectopic triglyceride storage closely related to clustering cardiometabolic risk factors. Hypertriglyceridemia; increased free fatty acid availability; adipose tissue release of proinflammatory cytokines; liver insulin resistance and inflammation; increased liver VLDL synthesis and secretion; reduced clearance of triglyceride-rich lipoproteins; presence of small, dense LDL particles; and reduced HDL cholesterol levels are among the many metabolic alterations closely related to this condition. Age, gender, genetics, and ethnicity are broad etiological factors contributing to variation in visceral adipose tissue accumulation. Specific mechanisms responsible for proportionally increased visceral fat storage when facing positive energy balance and weight gain may involve sex hormones, local cortisol production in abdominal adipose tissues, endocannabinoids, growth hormone, and dietary fructose. Physiological characteristics of abdominal adipose tissues such as adipocyte size and number, lipolytic responsiveness, lipid storage capacity, and inflammatory cytokine production are significant correlates and even possible determinants of the increased cardiometabolic risk associated with visceral obesity. Thiazolidinediones, estrogen replacement in postmenopausal women, and testosterone replacement in androgen-deficient men have been shown to favorably modulate body fat distribution and cardiometabolic risk to various degrees. However, some of these therapies must now be considered in the context of their serious side effects. Lifestyle interventions leading to weight loss generally induce preferential mobilization of visceral fat. In clinical practice, measuring waist circumference in addition to the body mass index could be helpful for the identification and management of a subgroup of overweight or obese patients at high cardiometabolic risk.

Pathophysiology of Human Visceral Obesity: An Update

Aging is associated with progressive loss of neuromuscular function that often leads to progressive disability and loss of independence. The term sarcopenia is now commonly used to describe the loss of skeletal muscle mass and strength that occurs in concert with biological aging. By the seventh and eighth decade of life, maximal voluntary contractile strength is decreased, on average, by 20-40% for both men and women in proximal and distal muscles. Although age-associated decreases in strength per unit muscle mass, or muscle quality, may play a role, the majority of strength loss can be accounted for by decreased muscle mass. Multiple factors lead to the development of sarcopenia and the associated impact on function. Loss of skeletal muscle fibers secondary to decreased numbers of motoneurons appears to be a major contributing influence, but other factors, including decreased physical activity, altered hormonal status, decreased total caloric and protein intake, inflammatory mediators, and factors leading to altered protein synthesis, must also be considered. The prevalence of sarcopenia, which may be as high as 30% for those ≥60 yr, will increase as the percentage of the very old continues to grow in our populations. The link between sarcopenia and disability among elderly men and women highlights the need for continued research into the development of the most effective interventions to prevent or at least partially reverse sarcopenia, including the role of resistance exercise and other novel pharmacological and nutritional interventions.

Invited review: Aging and sarcopenia.

ContextExercise is widely perceived to be beneficial for glycemic control and
weight loss in patients with type 2 diabetes. However, clinical trials on
the effects of exercise in patients with type 2 diabetes have had small sample
sizes and conflicting results.ObjectiveTo systematically review and quantify the effect of exercise on glycosylated
hemoglobin (HbA1c) and body mass in patients with type 2 diabetes.Data SourcesDatabase searches of MEDLINE, EMBASE, Sport Discuss, Health Star, Dissertation
Abstracts, and the Cochrane Controlled Trials Register for the period up to
and including December 2000. Additional data sources included bibliographies
of textbooks and articles identified by the database searches.Study SelectionWe selected studies that evaluated the effects of exercise interventions
(duration ≥8 weeks) in adults with type 2 diabetes. Fourteen (11 randomized
and 3 nonrandomized) controlled trials were included. Studies that included
drug cointerventions were excluded.Data ExtractionTwo reviewers independently extracted baseline and postintervention
means and SDs for the intervention and control groups. The characteristics
of the exercise interventions and the methodological quality of the trials
were also extracted.Data SynthesisTwelve aerobic training studies (mean [SD], 3.4 [0.9] times/week for
18 [15] weeks) and 2 resistance training studies (mean [SD], 10 [0.7] exercises,
2.5 [0.7] sets, 13 [0.7] repetitions, 2.5 [0.4] times/week for 15 [10] weeks)
were included in the analyses. The weighted mean postintervention HbA1c was lower in the exercise groups compared with the control groups
(7.65% vs 8.31%; weighted mean difference, −0.66%; P<.001). The difference in postintervention body mass between exercise
groups and control groups was not significant (83.02 kg vs 82.48 kg; weighted
mean difference, 0.54; P = .76).ConclusionExercise training reduces HbA1c by an amount that should
decrease the risk of diabetic complications, but no significantly greater
change in body mass was found when exercise groups were compared with control
groups.

https://jamanetwork.com/journals/jama/articlepdf/194184/JRV10001.pdf

Effects of Exercise on Glycemic Control and Body Mass in Type 2 Diabetes Mellitus: A Meta-analysis of Controlled Clinical Trials

Muscle mass and function are improved in the elderly during resistance exercise training. These improvements must result from alterations in the rates of muscle protein synthesis and breakdown. We determined the rate of quadriceps muscle protein synthesis using the in vivo rate of incorporation of intravenously infused [13C]leucine into mixed-muscle protein in both young (24 yr) and elderly (63-66 yr) men and women before and at the end of 2 wk of resistance exercise training. Before training, the fractional rate of muscle protein synthesis was lower in the elderly than in the young (0.030 +/- 0.003 vs. 0.049 +/- 0.004%/h; P = 0.004) but increased (P < 0.03) to a comparable rate of muscle protein synthesis in both young (0.075 +/- 0.009%/h) and elderly subjects (0.076 +/- 0.011%/h) after 2 wk of exercise. In the elderly, muscle mass, 24-h urinary 3-methylhistidine and creatinine excretion, and whole body protein breakdown rate determined during the [13C]leucine infusion were not changed after 2 wk of exercise. These findings demonstrate that, during the initial phase of a resistance exercise training program, a marked increase in quadriceps muscle protein synthesis rate occurs in elderly and young adults without an increase in the rate of whole body protein breakdown. In the elderly, this was not accompanied by an increase in urinary 3-methylhistidine excretion, an index of myofibrillar protein breakdown.

Acute effects of resistance exercise on muscle protein synthesis rate in young and elderly men and women

This experiment determined the amount of leptin required to correct different abnormalities in leptin-deficient ob/ob mice. Baseline food intakes and body weights of lean (+/?) and obese (ob/ob) C57B1/6J mice were recorded for 7 days. An Alzet miniosmotic pump was placed in the peritoneal cavity of each mouse and delivered 0, 1, 2, 5, 10, or 42 microg/day human leptin for 7 days. In ob/ob mice, 2 microg leptin/day reduced food intake and body weight, and increased hypothalamic and brain stem serotonin concentrations. All fat pads were reduced 35-40% by 10 microg leptin/day, and liver weight, lipid, and glycogen decreased. Serum insulin and glucose were reduced in all leptin-treated ob/ob mice, and levels were normalized by 10 microg/day leptin. Low rectal temperatures of ob/ob mice were corrected by 10 and 42 microg/day leptin. These doses also increased brown adipose tissue uncoupling protein expression. The only responses in lean mice were a transient reduction in food intake and weight loss with 10 or 42 microg/day leptin. This study shows enhanced leptin sensitivity in ob/ob mice and suggests that increased temperature and sympathetic activity are indirect responses to high concentrations of protein.

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A Leptin Dose-Response Study in Obese (ob/ob) and Lean (+/?) Mice

The purpose of this study was to determine whether growth hormone (GH) administration enhances the muscle protein anabolism associated with heavy-resistance exercise training in older men. Twenty-three healthy, sedentary men (67 +/- 1 yr) with low serum insulin-like growth factor I levels followed a 16-wk progressive resistance exercise program (75-90% max strength, 4 days/wk) after random assignment to either a GH (12.5-24 micrograms.kg-1.day-1; n = 8) or placebo (n = 15) group. Fat-free mass (FFM) and total body water increased more in the GH group. Whole body protein synthesis and breakdown rates increased in the GH group after treatment. However, increments in vastus lateralis muscle protein synthesis rate, urinary creatinine excretion, and training-specific isotonic and isokinetic muscle strength were similar in both groups, while 24-h urinary 3-methylhistidine excretion was unchanged after treatment. These observations suggest that resistance exercise training improved muscle strength and anabolism in older men, but these improvements were not enhanced when exercise was combined with daily GH administration. The greater increase in FFM with GH treatment may have been due to an increase in noncontractile protein and fluid retention.

Effect of growth hormone and resistance exercise on muscle growth and strength in older men

OBJECTIVE: To review the published literature regarding the effect of caloric restriction, pharmacologic intervention, and exercise to promote the loss of visceral adipose tissue (VAT) DESIGN: A review was conducted of published studies which measured VAT using computed tomography or magnetic resonance imaging before and after caloric restriction, pharmacologic therapy, or exercise. STUDIES REVIEWED: 23 separate studies were reviewed. Men represented 38% and women 63% of the 599 volunteers. There were 17 black volunteers and 30 patients with NIDDM included in these studies. MEASUREMENTS: Data regarding the baseline and change in VAT, body fat, and body weight were collected. RESULTS: Most interventions demonstrated a preferential loss of VAT regardless of the intervention applied. When expressed as percent change in VAT/percent change in body fat, a ratio can be calculated which we call the Selectivity Index (SI). When this index is applied to the literature reviewed, two observations can be made. First, the Selectivity Index is higher when baseline body fat is higher. Second, there is a direct relationship between the Selectivity Index and the baseline visceral fat ratio. These two observations suggest that individuals with greater visceral fat mass, either through an increase in the body weight or the propensity to store fat in the visceral depot, lose more visceral fat when adjusted to the loss of body fat. CONCLUSION: In conclusion, the Selectivity Index is useful to compare the ability of an intervention to specifically target the loss of AT. This simple index can serve as a benchmark for comparing intervention studies to each other.

Visceral adipose tissue: a critical review of intervention strategies.

This observational study was designed to determine whether football players with a history of heat cramps have elevated fluid and sodium losses during training. During a “two-a-day” training camp, five Division I collegiate football players (20.2 ± 1.6 y, 113 ± 20 kg) with history of heat cramps (C) were matched (weight, age, race and position) with a cohort of teammates (19.6 ± 0.6 y, 110 ± 20 kg) who had never cramped (NC). Change in body weight (adjusted by fluid intake) determined gross sweat loss. Sweat samples (forearm patch) were analyzed for sodium and potassium concentrations. Adlibitum fluid intake was measured by recording pre- and post-practice bottle weights. Average sweat sodium loss for a 2.5-h practice was projected at 5.1 ± 2.3 g (C) vs. 2.2 ± 1.7 g (NC). When averaged across two practices within the day, fluid intake was similar between groups (C: 2.6 ± 0.8 L vs. NC: 2.8 ± 0.7 L), as was gross sweat loss (C: 4.0 ± 1.1 L vs. NC: 3.5 ± 1.6 L). There was wide variability in the fluid defici...

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Jeffrey J. Zachwieja

Papers

Acute effects of resistance exercise on muscle protein synthesis rate in young and elderly men and women

A Leptin Dose-Response Study in Obese (ob/ob) and Lean (+/?) Mice

Effect of growth hormone and resistance exercise on muscle growth and strength in older men

Visceral adipose tissue: a critical review of intervention strategies.

Sweat and Sodium Losses in NCAA Football Players: A Precursor to Heat Cramps?