Subcutaneous adipose tissue accumulation protects systemic glucose tolerance and muscle metabolism

Abstract

The protective effects of lower body subcutaneous adiposity are linked to the depot functioning as a "metabolic sink" receiving and sequestering excess lipid. This postulate, however, is based on indirect evidence. Mechanisms that mediate this protection are unknown. Here we directly examined this with progressive subcutaneous adipose tissue removal. Ad libitum chow fed mice underwent sham surgery, unilateral or bilateral removal of inguinal adipose tissue or bilateral removal of both inguinal and dorsal adipose tissue. Subsequently mice were separated into 5 week chow or 5 or 13 week HFD groups (N = 10 per group). Primary outcome measures included adipocyte distribution, muscle and liver triglycerides, glucose tolerance, circulating adipocytokines and muscle insulin sensitivity. Subcutaneous adipose tissue removal caused lipid accumulation in femoral muscle proximal to excision, however, lipid accumulation was not proportionally inverse to adipose tissue quantity excised. Accumulative adipose removal was associated with an incremental reduction in systemic glucose tolerance in 13 week HFD mice. Although insulin-stimulated pAkt/Akt did not progressively decrease among surgery groups following 13 weeks of HFD, there was a suppressed pAkt/Akt response in the non-insulin stimulated (saline-injected) 13 week HFD mice. Hence, increases in lower body subcutaneous adipose removal resulted in incremental decreases in the effectiveness of basal insulin sensitivity of femoral muscle. The current data supports that the subcutaneous depot protects systemic glucose homeostasis while also protecting proximal muscle from metabolic dysregulation and lipid accumulation. Removal of the "metabolic sink" likely leads to glucose intolerance because of decreased storage space for glucose and/or lipids.

Unexpected Fat Distribution in Adolescents With Narcolepsy

“…Other research shows that removal of subcutaneous tissue through liposuction had no long-term effect on metabolic risk factors for coronary heart disease in obese women (65) and in one study even worsened postprandial blood lipid concentrations (66). These findings are supported and extended by research on murine models, where surgical removal of subcutaneous adipose tissue from high VAT animals caused a decrease in glucose tolerance and insulin sensitivity (67, 68). Reversely, transplanting of subcutaneous tissue into high VAT animals resulted in alleviation of diet induced metabolic disease (67, 69, 70).…”

Leptin in the regulation of the immunometabolism of adipose tissue-macrophages

“…It is known that the different depots of white adipose tissue have different biology and functions, with increments in the visceral adipose tissue (VAT) being strongly linked to adipocyte dysfunction, insulin resistance, and metabolic syndrome . On the other hand, subcutaneous adipose tissue (SAT, or also known as SQ WAT) is recognized for its greater capacity to store lipids and its contribution to proper glucose homeostasis . SAT buffers the excess fat, which otherwise would be toxic if in the circulation and accumulated ectopically or in VAT .…”

“…85,86 On the other hand, subcutaneous adipose tissue (SAT, or also known as SQ WAT) is recognized for its greater capacity to store lipids and its contribution to proper glucose homeostasis. 87 SAT buffers the excess fat, which otherwise would be toxic if in the circulation and accumulated ectopically or in VAT. 88 Consistently, insulin resistance is associated with lower levels of circulating leptin and reduced adipogenic capacity in the SAT of obese individuals, compared to insulin sensitive subjects.…”

Loss of STAT5 in adipocytes increases subcutaneous fat mass via sex-dependent and depot-specific pathways

“…Obesity is the primary disease of adipocytes and is a prominent risk factor for the development of type 2 diabetes mellitus (T2DM), cardiovascular disease, and certain cancers. However, some people with obesity are metabolically healthy (Stefan et al, 2018) and it is well-established that subcutaneous fat can have protective roles against metabolic dysfunction (Booth et al, 2018). Mouse models and humans with reduced growth hormone (GH) signaling have increased subcutaneous adiposity but improved metabolic health (Berryman et al, 2004;Coschigano et al, 2003;Dominici et al, 2002;Guevara-Aguirre et al, 2020a, 2020b.…”