Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons.
Kim. Seul Ki SK; Tran. Le Trung LT; NamKoong. Cherl C; Choi. Hyung Jin HJ; Chun. Hye Jin HJ; Lee. Yong-Ho YH; Cheon. MyungHyun M; Chung. ChiHye C; Hwang. Junmo J; Lim. Hyun-Ho HH; Shin. Dong Min DM; Choi. Yun-Hee YH; Kim. Ki Woo KW
Key Findings
- Systemic and brain‑area (ICV) delivery of SHLP2 prevented obesity in male mice on a high‑fat diet
- SHLP2 improved insulin sensitivity in these mice
- SHLP2 activated POMC neurons in the hypothalamus, reducing food intake and increasing thermogenesis
- SHLP2 was found to bind and activate the CXCR7 chemokine receptor
Practical Outcomes
- SHLP2 shows promise as a future tool for weight and metabolic control, but more research, especially in humans, is needed before any dosing or self‑administration protocols can be recommended.
Summary
A mouse study found that giving the peptide SHLP2, which is similar to humanin, helped protect against weight gain and improved insulin sensitivity on a high‑fat diet. It works by activating brain cells that curb appetite and boost heat production, and it appears to act through the CXCR7 receptor. However, the research is still early‑stage and only in animals, so it isn’t ready for direct use by people yet.
Abstract
Small humanin-like peptide 2 (SHLP2) is a mitochondrial-derived peptide implicated in several biological processes such as aging and oxidative stress. However, its functional role in the regulation of energy homeostasis remains unclear, and its corresponding receptor is not identified. Hereby, we demonstrate that both systemic and intracerebroventricular (ICV) administrations of SHLP2 protected the male mice from high-fat diet (HFD)-induced obesity and improved insulin sensitivity. In addition, the activation of pro-opiomelanocortin (POMC) neurons by SHLP2 in the arcuate nucleus of the hypothalamus (ARC) is involved in the suppression of food intake and the promotion of thermogenesis. Through high-throughput structural complementation screening, we discovered that SHLP2 binds to and activates chemokine receptor 7 (CXCR7). Taken together, our study not only reveals the therapeutic potential of SHLP2 in metabolic disorders but also provides important mechanistic insights into how it exerts its effects on energy homeostasis.
Study Information
pubmed
2023
2023-07-19T00:00:00.000Z
10.1038/s41467-023-40082-7
15
45