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Effects of Short-Term High Fat/ High Sugar Diet on Follicle - Stimulating Hormone Secretion and Ovarian Gene Expression

ABSTRACT: Obesity is associated with decreased reproductive fitness including changes in the hypothalamic-pituitary-gonadal axis. Exposure to high fat diet can impair reproductive function even in the absence of obesity. Here, we tested the effects of a short-term high fat/high sugar (HF/HS) diet on the secretion pattern of follicle-stimulating hormone (FSH) and changes in gene expression in mouse ovaries. We used Fshb null mice expressing either a wild-type human FSHB transgene by which FSH is released constitutively or those expressing a mutant human FSHB transgene by which FSH is re-routed and released from the regulated LH secretory pathway. Mice were maintained on a HF/HS diet or regular chow for 10 weeks and serial blood samples were collected from tail tips for FSH analyses. RNA-Seq analysis was used to determine changes in ovarian gene expression. After 10 weeks on HF/HS diet, the mice did not develop obesity and allowed us to study the effects on FSH secretion characteristics. While area under the curve for FSH was unchanged, the amplitude of FSH was altered in re-routed FSH expressing mice on a HF/HS diet. We identified distinct changes in ovarian gene expression depending on the diet (regular vs. HF/HS) and FSH secretion pattern (constitutive vs. re-routed). Overall, re-routed FSH expressing mice maintained better ovarian gene expression even when fed on HF/HS diet. Thus, our re-routed FSH expressing transgenic mice provide a trackable genetic model to study the long-term effects of HF/HS diet and other metabolic syndromes on FSH secretion characteristics and the consequences on ovarian function.

ORGANISM(S): Mus musculus

PROVIDER: GSE290347 | GEO | 2025/08/01

REPOSITORIES: GEO

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Project description:The human gut microbiota is an important metabolic organ, yet little is known about how its individual species interact, establish dominant positions, and respond to changes in environmental factors such as diet. In this study, gnotobiotic mice were colonized with an artificial microbiota comprising 12 sequenced human gut bacterial species and fed oscillating diets of disparate composition. Rapid, reproducible, and reversible changes in the structure of this assemblage were observed. Time-series microbial RNA-Seq analyses revealed staggered functional responses to diet shifts throughout the assemblage that were heavily focused on carbohydrate and amino acid metabolism. High-resolution shotgun metaproteomics confirmed many of these responses at a protein level. One member, Bacteroides cellulosilyticus WH2, proved exceptionally fit regardless of diet. Its genome encoded more carbohydrate active enzymes than any previously sequenced member of the Bacteroidetes. Transcriptional profiling indicated that B. cellulosilyticus WH2 is an adaptive forager that tailors its versatile carbohydrate utilization strategy to available dietary polysaccharides, with a strong emphasis on plant-derived xylans abundant in dietary staples like cereal grains. Two highly expressed, diet-specific polysaccharide utilization loci (PULs) in B. cellulosilyticus WH2 were identified, one with characteristics of xylan utilization systems. Introduction of a B. cellulosilyticus WH2 library comprising >90,000 isogenic transposon mutants into gnotobiotic mice, along with the other artificial community members, confirmed that these loci represent critical diet-specific fitness determinants. Carbohydrates that trigger dramatic increases in expression of these two loci and many of the organism’s 111 other predicted PULs were identified by RNA-Seq during in vitro growth on 31 distinct carbohydrate substrates, allowing us to better interpret in vivo RNA-Seq and proteomics data. These results offer insight into how gut microbes adapt to dietary perturbations at both a community level and from the perspective of a well-adapted symbiont with exceptional saccharolytic capabilities, and illustrate the value of artificial communities. An artificial community of 12 human gut bacterial species was introduced into germ-free male C57BL/6J mice at 10-12 weeks of age. Mice were split into two treatment groups, with each treatment group receiving an oscillating diet regimen in which animals were switched between a low fat, high plant polysaccharide (LF/HPP) diet and a high fat, high sugar (HF/HS) diet at two week intervals. One group was started on the LF/HPP diet, was switched to the HF/HS diet, and was then switched back to the LF/HPP diet. The other group was started on the HF/HS diet, was switched to the LF/HPP diet, and was then switched back to the HF/HS diet. Cecal contents were collected from each animal at the time of sacrifice which corresponded to the end of each treatment group's third diet phase. Separate gene expression profiles for each of the 12 species in the artificial community were generated for each sample using a series of custom mask files. 14 total samples (7 from animals consuming the LF/HPP diet at the time of sacrifice, 7 from animals consuming the HF/HS diet at the time of sacrifice). 12 gene expression profiles per sample (1/species).

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Effects of Short-Term High Fat/ High Sugar Diet on Follicle - Stimulating Hormone Secretion and Ovarian Gene Expression

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