Sex-dependent effects of a high fat diet on metabolic disorders, intestinal barrier function and gut microbiota in mouse

• Published in: Scientific reports 2024-08, Vol.14 (1), p.19835-16
• Main Authors: Lefebvre, Candice, Tiffay, Adam, Breemeersch, Charles-Edward, Dreux, Virginie, Bôle-Feysot, Christine, Guérin, Charlène, Breton, Jonathan, Maximin, Elise, Monnoye, Magali, Déchelotte, Pierre, Douard, Véronique, Goichon, Alexis, Coëffier, Moïse
• Format: Article
• Language: English
• Subjects: 631/326/2565/2134; 631/443/319/1642/393; Adipose tissue; Adipose Tissue, White - metabolism; Animals; Body composition; Body fat; Body Weight; Body weight gain; Cecum; Diet; Diet, High-Fat - adverse effects; Digestive system; Female; Females; Gastrointestinal Microbiome; Gastrointestinal tract; Gene expression; Glucose tolerance; High fat diet; Humanities and Social Sciences; Inflammation; Insulin Resistance; Intestinal Barrier Function; Intestinal microflora; Intestinal Mucosa - metabolism; Intestinal Mucosa - microbiology; Intestine; Life Sciences; Male; Males; Metabolic Diseases - etiology; Metabolic Diseases - metabolism; Metabolic Diseases - microbiology; Metabolic disorders; Metabolism; Mice; Mice, Inbred C57BL; Microbiota; Monocyte chemoattractant protein 1; multidisciplinary; Obesity - metabolism; Obesity - microbiology; Permeability; Relative abundance; Science; Science (multidisciplinary); Sex; Sex Factors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-70931-4

Obesity is often associated with sex-dependent metabolic complications, in which altered intestinal barrier function and gut microbiota contribute. We aimed to characterize in mice the sex-dependent effects of a high fat diet on these parameters. Male and female C57BL/6 mice received a standard (SD) or high fat diet (HFD; 60% kcal from fat) during 14 weeks (W14). Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic expression of 44 genes encoding factors involved in inflammatory response and gut barrier function, cecal microbiota, plasma adipokines and white adipose tissue response have been assessed. Both male and female HFD mice exhibited an increase of body weight and fat mass gain and glucose intolerance compared to SD mice. However, only male HFD mice tended to develop insulin resistance associated to increased Tnfα and Ccl2 mRNA expression in perigonadal adipose tissue. By contrast, only female HFD mice showed significant intestinal hyperpermeability that was associated with more markedly altered colonic inflammatory response. Cecal microbiota richness was markedly reduced in both sexes (Observed species) with sex-dependent modifications at the phyla or family level, e.g. decreased relative abundance of Bacillota and Lachnospiraceae in females, increased of Bacteroidaceae in males. Interestingly, some of these microbiota alterations were correlated with peripheral metabolic and inflammatory markers. In conclusions, male and female mice exhibit different responses to a high fat diet with specific changes of gut microbiota, intestinal barrier function, colonic and white adipose tissue inflammation, metabolic markers and body weight gain. The underlying mechanisms should be deciphered in further investigations.