Hairless (Hr) Deficiency Mitigates High-Fat Diet-Induced Obesity and Insulin Resistance in Mice

Obesity is a significant global health concern linked to excessive dietary energy intake. This research focuses on the mammalian hairless protein (HR), known for its role in skin and hair function, and its impact on metabolism. Examining male wild-type (Hr+/+) and Hr null (Hr-/-) mice over a 14-week normal chow diet (NCD) or high-fat diet (HFD) intervention. This study reveals that HR deficiency exhibited a protective effect against HFD-induced obesity and insulin resistance. This protective effect is attributed to increased energy expenditure in Hr-/- mice. Moreover, the brown adipose tissue (BAT) of Hr-/- mice displays elevated levels of the thermogenic protein, uncoupling protein 1 (Ucp1), and its key transcriptional regulators (PPAR gamma and PGC1 alpha), compared to Hr+/+ mice. In summary, the findings underscore the protective role of HR deficiency in countering HFD-induced adiposity by enhancing insulin sensitivity, raising energy expenditure, and augmenting thermogenic factors in BAT. Further exploration of HR metabolic regulation holds promise for potential therapeutic targets in addressing obesity-related metabolic disorders. This study reveals that HR deficiency in mice leads to reduced adiposity, improved insulin sensitivity, and enhanced energy expenditure under a high-fat diet, potentially via increased thermogenic factors in brown adipose tissue. These findings suggest HR's pivotal role in energy metabolism and its potential as a therapeutic target for obesity-related disorders. image