The aim of this article is to investigate the relationship between obesity and adipose tissue accumulation and the pathways involved in the development of muscle atrophy, where aberrant lipid accumulation in organs may affect peripheral insulin sensitivity and decrease muscle mass. Insulin resistance (IR) and muscle mass loss often occur concomitantly in individuals with type 2 diabetes (T2D). Most patients with type 2 diabetes are overweight, and it is well established that obesity and impaired lipid metabolism play an important role in the development of IR in these individuals. In particular, increased adipose tissue mass and dysfunction in adipose tissue lead to fat accumulation and systemic inflammation through altered adipose secretions and factors and cytokines. In addition, increased fatty acid flow from adipose tissue may lead to increased fat storage in the liver and skeletal muscle, thus resulting in altered hepatic secretions, mitochondrial function, and impaired insulin signaling in skeletal muscle. Therefore, obesity and adipose tissue disorders can lead to muscle atrophy, which causes IR and are two sides of the same coin with muscle atrophy. However, the exact relationship between lipid accumulation, T2D, and muscle atrophy is largely unknown and requires further investigation in this area.