MOTS-c is a 16-amino acid peptide encoded from 12S rRNA region of the mitochondrial DNA [1]. Multiple publications support the notion that MOTS-c plays an important role in regulating metabolism and insulin action and it has been suggested that MOTS-c exerts exercise mimetic effects in rodents [2]. In this issue of the Journal of Molecular Medicine, Lu et al.[3] revealed an important new role of MOTS-c as a hormone capable of preventing negative metabolic effects associated with menopause in an ovariectomized mouse model. These investigators found that MOTS-c treatment reduced both the weight gain as well as the insulin resistance associated with experimental menopause. Furthermore, they found that MOTS-c also suppressed the increase in inflammatory markers such as IL-1ß and IL-6 in adipose tissue. This antiinflammatory effect may be a key in the health-promoting effects of MOTS-c.

It is well known that postmenopausal women exhibit physiological alterations including weight gain, changes in adipose tissue distribution, and deterioration of insulin secretion, and sensitivity [4, 5]. These changes predispose them to develop type 2 diabetes [4]. Furthermore, decreased levels of estrogen are associated with non-alcoholic steatohepatitis, osteoporosis, and cardiovascular diseases [6–8]. These menopausalassociated metabolic abnormalities and health problems can be alleviated by exercise, whose benefits are obtained via diverse mechanisms including decreased inflammatory mediators, increased activity of antioxidants, and improved endothelial function [9, 10]. A recent meta-analysis on the effects of programmed exercise on insulin sensitivity-related outcomes in postmenopausal women revealed that exercising for 3 to 4 months significantly lowers insulin levels, and improves HOMA-IR, BMI, waist circumference, and body fat mass [11]. Exercise, which induces muscle remodeling, is beneficial not only for menopause but also for multiple other