Desacetyl-\u03b1-MSH and \u03b1-MSH have sex specific interactions with diet to influence mouse gut morphology, metabolites and microbiota

Bo Sun,Elizabeth Mckenzie,Rinki Murphy,Tommi Vatanen,Justin M O'Sullivan,Thilini N Jayasinghe

doi:10.1038/s41598-020-75786-z

Bo Sun, Elizabeth Mckenzie + Show 4 more

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https://doi.org/10.1038/s41598-020-75786-z

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Journal: Scientific Reports	Publication Date: Nov 3, 2020
Citations: 3	License type: open-access

Affiliation: University of Auckland, Maurice Wilkins Centre

Abstract

The melanocortin peptides have an important role in regulating body weight and appetite. Mice that lack the desacetyl-α-MSH and α-MSH peptides (Pomctm1/tm1) develop obesity. This effect is exacerbated by a high fat diet (HFD). However, development of obesity in female Pomctm1/tm1 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 Pomctm1/tm1 mice lacked this adaptation to a chronic HFD. Both Pomctm1/tm1 genotype and chronic HFD were significantly associated with gut microbiota composition. Sex-specific associations between Pomctm1/tm1 genotype and gut microbiota were observed in the presence of a chronic HFD. Pomctm1/tm1 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.

Highlights

The melanocortin system is central to body weight regulation, influencing feeding behavior, energy expenditure, glucose control, and lipid m etabolism[1,2]
While this was attributed to impaired adaptive t hermogenesis[6], an alternative/ complementary hypothesize could be that desacetyl-α-MSH and α-MSH produce the sexually dimorphic response to chronic high fat (HF) diet by promoting gut energy extraction in female Pomctm1/tm[1] mice, which takes time to d evelop[6]
The observed difference in small intestine length was statistically significant in Pomctm1/tm[1] mice maintained on a chronic HF diet (Fig. 2A male: p = 0.0477 and B female: p = 0.0473) where it was proportional to increased body length, as observed previously[6]

Summary

Introduction

The melanocortin system is central to body weight regulation, influencing feeding behavior, energy expenditure, glucose control, and lipid m etabolism[1,2]. C57BL/6J female mice are protected from diet-induced obesity, partly due to a reduction in food intake[6] This sexually dimorphic response to the HF diet is not observed in Pomctm1/tm1 mice[6]. The obesity phenotype observed in female Pomctm1/tm[1] mice fed a chronic HF diet was greater than the increase in food intake predicted[6] While this was attributed to impaired adaptive t hermogenesis[6], an alternative/ complementary hypothesize could be that desacetyl-α-MSH and α-MSH produce the sexually dimorphic response to chronic HF diet by promoting gut energy extraction in female Pomctm1/tm[1] mice, which takes time to d evelop[6]. Consistent with this, shorter and thicker microvilli, increased enterocyte counts, and increased nutrient absorption have been observed in rat intestines in response to a HF diet[15]

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