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Yuzbashian, E.* ; Fernando, D.N.* ; Jacobs, R.L.* ; Lesker, T.* ; Strowig, T.* ; Ussar, S. ; Chan, C.B.*

A comparison of the effects of milk, yogurt, and cheese on insulin sensitivity, hepatic steatosis, and gut microbiota in diet-induced obese male mice.

Int. J. Mol. Sci. 26, 5026 - 5026 (2025)

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The effects of low-fat dairy products on insulin resistance (IR), hepatic steatosis, and gut microbiota composition in high-fat diet (HFD)-fed obese mice were examined. C57BL/6 male mice (n = 16/group) were fed a high-fat diet (HFD, 45% fat) or HFD supplemented with either fat-free milk (MILK), fat-free yogurt (YOG), or reduced-fat (19% milk fat) cheddar cheese (CHE) at 10% of the total energy intake for 8 weeks. Body weight, fat mass, liver lipids, and metabolic enzymes were evaluated. Compared with HFD, MILK reduced homeostatic assessment of insulin resistance along with increased hepatic insulin signaling and decreased hepatic gluconeogenic enzymes. YOG and MILK decreased hepatic triacylglycerol content and lipid droplet size, while CHE had no effect. In the liver, MILK and YOG downregulated de novo lipogenesis enzymes. In MILK, fat oxidation capacity was elevated. Compared with HFD, liver lipidomic analysis in MILK and YOG revealed unique profiles of decreased proinflammatory lipid species, including ceramides. Dairy feeding elicited an increase in beneficial bacteria, such as Streptococcus in YOG and Anaero-tignum in MILK, as shown by 16S rRNA sequencing of gut microbiota. In conclusion, the ability of milk and yogurt to reduce hepatic steatosis in HFD mice may be explained, at least in part, by the regulation of the gut microbiome and liver lipidome.

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