Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
The Liggins Institute, University of Auckland, 85 Park Road, Grafton, Auckland, 1142, New Zealand.
Sci Rep. 2020 Nov 3;10(1):18957. doi: 10.1038/s41598-020-75786-z.
The melanocortin peptides have an important role in regulating body weight and appetite. Mice that lack the desacetyl-α-MSH and α-MSH peptides (Pomc) develop obesity. This effect is exacerbated by a high fat diet (HFD). However, development of obesity in female Pomc mice during chronic HFD conditions is not fully accounted for by the increased energy intake. We hypothesized that the protection against chronic HFD-induced obesity imparted by MSH peptides in females is mediated by sex-specific alterations in the gut structure and gut microbiota. We determined that female WT mice had reduced jejunum villus length and increased crypt depth in response to chronic HFD. WT males and Pomc mice lacked this adaptation to a chronic HFD. Both Pomc genotype and chronic HFD were significantly associated with gut microbiota composition. Sex-specific associations between Pomc genotype and gut microbiota were observed in the presence of a chronic HFD. Pomc females had significantly reduced fecal acetate and propionate concentrations when compared to WT females. We conclude that MSH peptides influence jejunum villus length, crypt depth and the structure of the gut microbiota. These effects favor reduced nutrient absorption and occur in addition to the recognized roles of desacetyl-α-MSH and α-MSH peptides in appetite control.
黑素细胞刺激素肽在调节体重和食欲方面发挥着重要作用。缺乏去乙酰-α-MSH 和 α-MSH 肽（Pomc）的小鼠会发展为肥胖。高脂肪饮食（HFD）会使这种情况恶化。然而，在慢性 HFD 条件下，雌性 Pomc 小鼠的肥胖发展并不能完全归因于能量摄入的增加。我们假设，MSH 肽在雌性中对慢性 HFD 诱导的肥胖的保护作用是通过肠道结构和肠道微生物群的性别特异性改变来介导的。我们发现，慢性 HFD 会导致 WT 雌性小鼠空肠绒毛长度缩短和隐窝深度增加。WT 雄性和 Pomc 小鼠缺乏这种对慢性 HFD 的适应。Pomc 基因型和慢性 HFD 都与肠道微生物群组成显著相关。在存在慢性 HFD 的情况下，观察到 Pomc 基因型和肠道微生物群之间存在性别特异性关联。与 WT 雌性相比，Pomc 雌性的粪便乙酸盐和丙酸盐浓度显著降低。我们得出结论，MSH 肽影响空肠绒毛长度、隐窝深度和肠道微生物群的结构。这些影响有利于减少营养物质的吸收，并且除了去乙酰-α-MSH 和 α-MSH 肽在食欲控制中的作用外，还存在这些作用。
