Recent studies have extended our understanding of the role of leptin in obesity and diabetes. The findings suggest there is a close association between leptin and the age-related changes in body composition that occur with sarcopenia or sarcopenic obesity, a condition that involves deteriorating insulin resistance and diabetes [43, 44]. Several studies have indicated that elevated leptin levels are associated with sarcopenia independent of obesity in adult humans [51, 52]. In a rodent model of obesity and diabetes, muscle regeneration was impaired following muscle injury because of the diminished proliferation and differentiation of satellite cells, tissue-resident stem cells in skeletal muscle [57, 59, 62]. Several studies in rodents have indicated that leptin signaling plays an important role in promoting skeletal muscle regeneration through the regulation of several proteins [66–68] and microRNAs [69] linked to muscle growth, cell cycle progression, and protein catabolism. Thus, the loss of functional leptin signaling might negatively impact skeletal muscle regeneration and contribute to sarcopenia in obesity and diabetes (Fig. 14.2).

Despite marked progress in recent years toward understanding the regulatory role of leptin in skeletal muscle lipid accumulation and glucose homeostasis, several questions pertaining to leptin’s potential therapeutic use in patients with obesity and/or diabetes remain to be answered. For example, does leptin resistance occur at the local level of skeletal muscle, and, if so, how does it develop in skeletal muscle during obesity? The fact that impairment of the regenerative capacity of muscle satellite cells has been observed only in extremely obese mice in which leptin activity was genetically ablated (ob/ob and db/db) is another important issue [66–68]. Further investigation is warranted to elucidate whether moderate impairment of leptin action, commonly observed in diet-induced obesity, affects the regenerative capacity of skeletal muscle in humans and to identify factors or signaling pathways that link muscle lipid accumulation and impaired satellite cell function in the context of leptin resistance. Given the information currently available, exercise [60] and caloric restriction [61, 72] might be promising ways to enhance skeletal muscle fatty acid oxidation and promote skeletal muscle mass maintenance via the regeneration of satellite cells in obese and diabetic patients with leptin resistance. Continued advances are expected to improve our understanding of leptin’s effects on glucose/lipid metabolism and skeletal muscle mass maintenance and to facilitate the therapeutic use of leptin in the treatment of human obesity and diabetes.