Nutrient-sensing growth hormone secretagogue receptor in macrophage programming and meta-inflammation

Kim, Da Mi; Lee, Jong Han; Pan, Quan; Han, Hye Won; Shen, Zheng; Eshghjoo, Sahar; Wu, Chia-Shan; Yang, Wanbao; Noh, Ji Yeon; Threadgill, David W.; Guo, Shaodong; Wright, Gus; Alaniz, Robert; Sun, Yuxiang

doi:10.1016/j.molmet.2023.101852

Cited by 5 publications

(1 citation statement)

References 132 publications

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“…Variable results have been reported for global GHSR deletion mice in DIO; some studies showed no difference in weight gain under a high-fat diet (HFD) [32,33], whereas others showed a decrease in weight gain [34]. GHSR is also known for its association with aging, and we previously reported that the ablation of GHSR suppresses age-related changes in adipose/hepatic inflammation and insulin resistance, and we recently reported that macrophage GHSR controls systemic inflammation and insulin resistance in DIO [35][36][37][38][39][40].…”

Section: Introductionmentioning

confidence: 99%

GHSR Deletion in β-Cells of Male Mice: Ineffective in Obesity, but Effective in Protecting against Streptozotocin-Induced β-Cell Injury in Aging

Han,

Pradhan,

Villarreal

et al. 2024

Nutrients

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Insulin secretion from pancreatic β cells is a key pillar of glucose homeostasis, which is impaired under obesity and aging. Growth hormone secretagogue receptor (GHSR) is the receptor of nutrient-sensing hormone ghrelin. Previously, we showed that β-cell GHSR regulated glucose-stimulated insulin secretion (GSIS) in young mice. In the current study, we further investigated the effects of GHSR on insulin secretion in male mice under diet-induced obesity (DIO) and streptozotocin (STZ)-induced β-cell injury in aging. β-cell-specific-Ghsr-deficient (Ghsr-βKO) mice exhibited no glycemic phenotype under DIO but showed significantly improved ex vivo GSIS in aging. We also detected reduced insulin sensitivity and impaired insulin secretion during aging both in vivo and ex vivo. Accordingly, there were age-related alterations in expression of glucose transporter, insulin signaling pathway, and inflammatory genes. To further determine whether GHSR deficiency affected β-cell susceptibility to acute injury, young, middle-aged, and old Ghsr-βKO mice were subjected to STZ. We found that middle-aged and old Ghsr-βKO mice were protected from STZ-induced hyperglycemia and impaired insulin secretion, correlated with increased expression of insulin signaling regulators but decreased pro-inflammatory cytokines in pancreatic islets. Collectively, our findings indicate that β-cell GHSR has a major impact on insulin secretion in aging but not obesity, and GHSR deficiency protects against STZ-induced β-cell injury in aging.

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