Allen DL, Cleary AS, Speaker KJ, Lindsay SF, Uyenishi J, Reed JM, Madden MC, Mehan RS. Myostatin, activin receptor IIb, and follistatin-like-3 gene expression are altered in adipose tissue and skeletal muscle of obese mice. Am J Physiol Endocrinol Metab 294: E918-E927, 2008. First published March 11, 2008 doi:10.1152/ajpendo.00798.2007 is a secreted growth inhibitor expressed in muscle and adipose. We sought to determine whether expression of MSTN, its receptor activin RIIb (ActRIIb), or its binding protein follistatin-like-3 (FSTL3) are altered in subcutaneous or visceral adipose or in skeletal muscle in response to obesity. MSTN and ActRIIb mRNA levels were low in subcutaneous (SQF) and visceral fat (VF) from wild-type mice but were 50-to 100-fold higher in both SQF and VF from ob/ob compared with wild-type mice. FSTL3 mRNA levels were increased in SQF but decreased in VF in ob/ob compared with wild-type mice. Moreover, MSTN mRNA levels were twofold greater in tibialis anterior (TA) from ob/ob mice, whereas ActRIIb and FSTL3 mRNA levels were unchanged. MSTN mRNA levels were also increased in TA and SQF from mice on a high-fat diet. Injection of ob/ob mice with recombinant leptin caused FSTL3 mRNA levels to decrease in both VF and SQF in ob/ob mice; MSTN and ActRIIb mRNA levels tended to decrease only in VF. Finally, MSTN mRNA levels and promoter activity were low in adipogenic 3T3-L1 cells, but an MSTN promoter-reporter construct was activated in 3T3-L1 cells by cotransfection with the adipogenic transcription factors SREBP-1c, C/EBP␣, and PPAR␥. These results demonstrate that expression of MSTN and its associated binding proteins can be modulated in adipose tissue and skeletal muscle by chronic obesity and suggest that alterations in their expression may contribute to the changes in growth and metabolism of lean and fat tissues occurring during obesity. leptin; 3T3-L1 cells; visceral adipose tissue; subcutaneous adipose tissue FACTORS THAT AFFECT THE GROWTH of skeletal muscle or of adipose tissue can have profound effects on overall health and viability (18). One such factor regulating growth of skeletal muscle and adipose is myostatin (MSTN). MSTN is a member of the activin/transforming growth factor-␤ (TGF␤)/bone morphogenetic protein (BMP) family of secreted signaling factors that binds to the activin receptor type II family members, most notably activin receptor IIb (ActRIIb; Ref. 20), and inhibits skeletal muscle growth through repression of proliferation, differentiation, and protein synthesis (33, 37). Inactivating mutations to the MSTN gene result in a hypermuscular phenotype in mice, cows, and humans (15,25,36), whereas muscle-specific overexpression of MSTN in transgenic mice results in decreased muscle mass (31).In addition, several lines of evidence have suggested a role for MSTN in the regulation of adipose tissue growth in addition to its obvious effects on muscle growth. First, in their initial paper identifying the MSTN gene, McPherron et al. (25) stated that MSTN mRNA could be detected by ...

To prime local tissues for dealing with potential infection or injury, exposure to an acute, intense stressor evokes increases in circulating and local tissue inflammatory proteins. Regular physical activity facilitates stress-evoked innate reactivity and modulates the expression of inflammatory proteins in immuno-metabolic tissues such as white adipose tissue (WAT). The impact of regular physical activity on stress-evoked inflammatory protein expression in WAT, however, remains unclear. To investigate this question, lean male F344 rats (150–175 g) were allowed voluntary access to a running wheel for 6 weeks followed by exposure to an acute stressor (100, 1.5 mA-5 s inescapable tail shocks). Using ELISAs, corticosterone, heat shock protein 72 (Hsp72), macrophage chemoattractant protein (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, and IL-10 concentrations were measured in plasma and subcutaneous, intraperitoneal (epididymal and retroperitoneal WAT depots) and visceral (omental and mesenteric WAT depots) WAT compartments. Acute stress increased plasma concentrations of all proteins except TNF-α and, depending upon the compartment examined, WAT concentrations of MCP-1, IL-1β, IL-6, and IL-10. Exercise ubiquitously increased IL-1β within WAT, potentiated stress-evoked Hsp72 in plasma and WAT, and differentially increased stress-evoked MCP-1, IL-6, and IL-10 within WAT. These data suggest: (a) inflammatory proteins in non-obese WAT may serve compartment-specific immune and metabolic roles important to the acute stress response and; (b) voluntary habitual exercise may optimize stress-induced augmentation of innate immune function through increases in stress-evoked Hsp72, MCP-1, IL-6, and IL-10 and decreases in IL-1β/IL10 and TNF-α/IL10 ratios within white adipose tissue.

BackgroundA disproportionate amount of body fat within the abdominal cavity, otherwise known as visceral obesity, best predicts the negative health outcomes associated with high levels body fat. Growing evidence suggests that repeated activation of the stress response can favor visceral fat deposition and that visceral obesity may induce low-grade, systemic inflammation which is etiologically linked to the pathogenesis of obesity related diseases such as cardiovascular disease and type 2 diabetes. While the obesity epidemic has fueled considerable interest in these obesity-related inflammatory diseases, surprisingly little research is currently focused on understanding the functions of inflammatory proteins in healthy, non-obese white adipose tissue (WAT) and their possible role in modulating stress-induced shifts in body fat distribution.HypothesisThe current review presents evidence in support the novel hypothesis that stress-evoked interleukin-1 beta (IL-1β) signaling within subcutaneous adipose tissue, when repeatedly induced, contributes toward the development of visceral obesity. It is suggested that because acute stressor exposure differentially increases IL-1β levels within subcutaneous adipose relative to visceral adipose tissue in otherwise healthy, non-obese rats, repeated induction of this response may impair the ability of subcutaneous adipose tissue to uptake energy substrates, synthesize and retain triglycerides, and/or adapt to positive energy balance via hyperplasia. Consequently, circulating energy substrates may be disproportionately shunted to visceral adipose tissue for storage, thus driving the development of visceral obesity.ConclusionsThis review establishes the following key points: 1) body fat distribution outweighs the importance of total body fat when predicting obesity-related disease risk; 2) repeated exposure to stress can drive the development of visceral obesity independent of changes in body weight; 3) because of the heterogeneity of WAT composition and function, an accurate understanding of WAT responses requires sampling multiple WAT depots; 4) acute, non-pathogenic stressor exposure increases WAT IL-1β concentrations in a depot specific manner suggesting an adaptive, metabolic role for this cytokine; however, when repeated, stress-induced IL-1β in non-visceral WAT may result in functional impairments that drive the development of stress-induced visceral obesity.

SummaryObjectiveThe objective of this randomized equivalence trial was to determine the impact of consuming lean beef as part of a high protein (HP) weight‐reducing diet on changes in body weight, body composition and cardiometabolic health.MethodsA total of 120 adults (99 female) with overweight or obesity (BMI: 35.7 ± 7.0 kg m−2) were randomly assigned to consume either a HP diet with ≥4 weekly servings of lean beef (B; n = 60) or a HP diet restricted in all red meats (NB; n = 60) during a 16‐week weight loss intervention.ResultsBody weight was reduced by 7.8 ± 5.9% in B and 7.7 ± 5.5% in NB (p < 0.01 for both). Changes in percent body weight were equivalent between B and NB (mean difference: 0.06%, 90% confidence interval: (−1.7, 1.8)). Fat mass was reduced in both groups (p < 0.01; B: 8.0 ± 0.6 kg, NB: 8.6 ± 0.6 kg), while lean mass was not reduced in either group. Improvements in markers of cardiometabolic health (total cholesterol, low‐density lipoprotein cholesterol, triglycerides and blood pressure) were not different between B and NB.ConclusionResults of this study demonstrate that HP diets – either rich or restricted in red meat intakes – are effective for decreasing body weight and improving body composition and cardiometabolic health.

No abstract

Sterile inflammation occurs when inflammatory proteins are increased in blood and tissues by nonpathogenic states and is a double-edged sword depending on its cause (stress, injury, or disease), duration (transient versus chronic), and inflammatory milieu. Short-term fasting can exert a host of health benefits through unknown mechanisms. The following experiment tested if a 24 h fast would modulate basal and stress-evoked sterile inflammation in plasma and adipose. Adult male F344 rats were either randomized to ad libitum access to food or fasted for 24 h prior to 0 (control), 10, or 100, 1.5 mA-5 s intermittent, inescapable tail shocks (IS). Glucose, nonesterified free fatty acids (NEFAs), insulin, leptin, and corticosterone were measured in plasma and tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, IL-6, and IL-10 in plasma, and subcutaneous, intraperitoneal, and visceral compartments of white adipose tissue (WAT). In control rats, a 24 h fast reduced all measured basal cytokines in plasma and visceral WAT, IL-1β and IL-6 in subcutaneous WAT, and IL-6 in intraperitoneal WAT. In stressed rats (IS), fasting reduced visceral WAT TNF-α, subcutaneous WAT IL-1β, and plasma insulin and leptin. Short-term fasting may thus prove to be a useful dietary strategy for reducing peripheral inflammatory states associated with visceral obesity and chronic stress.

SummaryObjectiveThis 12‐month randomized, non‐inferiority clinical trial sought to determine the impact of consuming soy protein as part of an energy‐restricted, high‐protein diet on weight loss, body composition and cardiometabolic health.MethodsSeventy‐one adults (58 female) with overweight or obesity (body mass index: 32.9 ± 3.6 kg m−2) were randomly assigned to consume three servings of soy (S) or non‐soy (NS) protein foods per day for 12 months. All participants completed a group‐based behavioural weight loss program lasting 4 months (M4), and follow‐up assessments were completed at month 12 (M12).ResultsBody weight was reduced in both groups at M4 (S: −7.0% ± 5.2%, NS: −7.1% ± 5.7%) and M12 (S: 3.6% ± 5.1%, NS: −4.8% ± 7.3%). Body weight reductions (mean difference [90% confidence interval]) were not different between S and NS at either time point (M4: −0.16% [−1.4, 3.6], P = 0.90; M12: 1.1% [−1.4, 3.6], P = 0.44). Differences in body fat mass loss were not different between S and NS at M4 (0.29 ± 0.84 kg, P = 0.73) or M12 (0.78 ± 1.5 kg, P = 0.59). Weight loss‐induced improvements in cholesterol, triglycerides and blood pressure did not differ between S and NS.ConclusionThese results indicate that soy‐based protein foods can be effectively incorporated into an energy‐restricted, high‐protein diet for improving body weight, body composition and cardiometabolic health.

No abstract