Short-term weight loss attenuates local tissue inflammation and improves insulin sensitivity without affecting adipose inflammation in obese mice

Abstract

Obesity is a major cause of insulin resistance, and weight loss is shown to improve glucose homeostasis. But the underlying mechanism and the role of inflammation remain unclear. Male C57BL/6 mice were fed a high-fat diet (HFD) for 12 wk. After HFD, weight loss was induced by changing to a low-fat diet (LFD) or exercise with continuous HFD. The weight loss effects on energy balance and insulin sensitivity were determined using metabolic cages and hyperinsulinemic euglycemic clamps in awake mice. Diet and exercise intervention for 3 wk caused a modest weight loss and improved glucose homeostasis. Weight loss dramatically reduced local inflammation in skeletal muscle, liver, and heart but not in adipose tissue. Exercise-mediated weight loss increased muscle glucose metabolism without affecting Akt phosphorylation or lipid levels. LFD-mediated weight loss reduced lipid levels and improved insulin sensitivity selectively in liver. Both weight loss interventions improved cardiac glucose metabolism. These results demonstrate that a short-term weight loss with exercise or diet intervention attenuates obesity-induced local inflammation and selectively improves insulin sensitivity in skeletal muscle and liver. Our findings suggest that local factors, not adipose tissue inflammation, are involved in the beneficial effects of weight loss on glucose homeostasis.

Altered Interleukin-10 Signaling in Skeletal Muscle Regulates Obesity-Mediated Inflammation and Insulin Resistance

“…In fact, recent studies indicate that obesity-mediated inflammation and macrophage accumulation develop in multiple organs, including skeletal muscle, liver, pancreas, heart, and brain (9)(10)(11)(12)(13). In that regard, our recent study found that exercise-mediated weight loss improved insulin action without affecting adipose tissue inflammation in mice with diet-induced obesity (7). Additionally, improved insulin action following weight loss was associated with reduced local inflammation in skeletal muscle, suggesting an important role of muscle inflammation in obesity-mediated insulin resistance (7).…”

“…In that regard, our recent study found that exercise-mediated weight loss improved insulin action without affecting adipose tissue inflammation in mice with diet-induced obesity (7). Additionally, improved insulin action following weight loss was associated with reduced local inflammation in skeletal muscle, suggesting an important role of muscle inflammation in obesity-mediated insulin resistance (7). These findings clearly contest the adipocentric view of insulin resistance.…”

“…Obesity is characterized by altered levels of circulating cytokines, and adipose tissue macrophage accumulation and inflammation have been causally associated with insulin resistance (5,6). However, recent studies have challenged this earlier notion on the causal role of adipose tissue macrophages and inflammation in the development of insulin resistance (7,8).…”

Roles of Exosome-Like Vesicles Released from Inflammatory C2C12 Myotubes: Regulation of Myocyte Differentiation and Myokine Expression

“…WAT is a source of obesity-induced chronic inflammation [1]; however, it is not the only organ that develops macrophage accumulation in obesity. In fact, recent studies have challenged the causal role of WAT inflammation in obesity-linked metabolic dysregulation of the whole body [2,3]. In addition, it was suggested that local inflammation and ectopic lipid accumulation in skeletal muscle leads to impaired insulin signaling [2].…”

“…In fact, recent studies have challenged the causal role of WAT inflammation in obesity-linked metabolic dysregulation of the whole body [2,3]. In addition, it was suggested that local inflammation and ectopic lipid accumulation in skeletal muscle leads to impaired insulin signaling [2]. Furthermore, inflammation in skeletal muscle and the accumulation of macrophages are observed not only in metabolic diseases but also in certain conditions, such as aged muscle [4], acute muscle damage by high-intensity eccentric exercise [5,6], or chronic diseases (including cancer cachexia) [7], which leads to physical inactivity and aggravates the loss of skeletal muscle oxidative capacity, and vice versa [8].…”