Lipotoxicity plays a key role in the development of both insulin resistance and muscle atrophy in patients with type 2 diabetes

• Published in: Obesity reviews Vol. 20; no. 9; pp. 1205 - 1217
• Main Authors: Meex, Ruth C.R., Blaak, Ellen E., Loon, Luc J.C.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.09.2019; John Wiley and Sons Inc
• Subjects: Accumulation; adipokines; Adipose tissue; Atrophy; Body weight; Cytokines; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Fatty acids; hormone secretion; Humans; inflammation; Insulin; Insulin resistance; Insulin Resistance - physiology; interorgan crosstalk; Lipid metabolism; Lipid Metabolism - physiology; Lipids; lipotoxicity; liver; Mitochondria; muscle atrophy; Muscle, Skeletal - metabolism; Muscles; muscular atrophy; Muscular Atrophy - etiology; Muscular Atrophy - pathology; Musculoskeletal system; noninsulin-dependent diabetes mellitus; Obesity; Obesity - metabolism; Obesity - physiopathology; Obesity Comorbidity/Etiology and Pathophysiology; Organs; Overflow; Overweight; patients; Signal transduction; Skeletal muscle; muscle atrophy; interorgan crosstalk; insulin resistance; obesity
• ISSN: 1467-7881; 1467-789X; 1467-789X
• DOI: 10.1111/obr.12862

Summary Insulin resistance and muscle mass loss often coincide in individuals with type 2 diabetes. Most patients with type 2 diabetes are overweight, and it is well established that obesity and derangements in lipid metabolism play an important role in the development of insulin resistance in these individuals. Specifically, increased adipose tissue mass and dysfunctional adipose tissue lead to systemic lipid overflow and to low‐grade inflammation via altered secretion of adipokines and cytokines. Furthermore, an increased flux of fatty acids from the adipose tissue may contribute to increased fat storage in the liver and in skeletal muscle, resulting in an altered secretion of hepatokines, mitochondrial dysfunction, and impaired insulin signalling in skeletal muscle. Recent studies suggest that obesity and lipid derangements in adipose tissue can also lead to the development of muscle atrophy, which would make insulin resistance and muscle atrophy two sides of the same coin. Unfortunately, the exact relationship between lipid accumulation, type 2 diabetes, and muscle atrophy remains largely unexplored. The aim of this review is to discuss the relationship between type 2 diabetes and muscle loss and to discuss some of the joint pathways through which lipid accumulation in organs may affect peripheral insulin sensitivity and muscle mass.