Camel milk is associated with ameliorated high-fat diet-induced obesity and metabolic disorders via modulation of gut microbiota and remodeling of hepatic lipid metabolism: a multi-omics analysis
TL;DR
It is suggested that camel milk attenuates HFD-induced obesity and associated metabolic disturbances in association with gut microbiota modulation, enhanced SCFA production, and remodeling of hepatic lipid metabolism involving the gut-liver axis, pointing to CM as a potential dietary intervention for obesity management.
Abstract
This study investigated the therapeutic effects of camel milk (CM) on high-fat diet (HFD)-induced obesity and its underlying mechanisms through integrative multi-omics analysis. C57BL/6J mice were fed a normal diet (NC), an HFD, or an HFD supplemented with CM via intragastric administration for 7 weeks, with orlistat as a positive control. CM treatment significantly reduced body weight, inguinal and epididymal white adipose tissue weights, serum triglyceride and LDL-C levels, and adipocyte hypertrophy compared to the HFD group. Additionally, CM ameliorated HFD-induced hepatic injury, as evidenced by reduced serum ALT levels and attenuated hepatic steatosis. 16S rRNA gene sequencing revealed that CM partially reversed HFD-induced gut microbiota dysbiosis, characterized by increased Bacteroidota abundance, suppression of pro-inflammatory genera (Mucispirillum, Escherichia-Shigella, Faecalitalea), and enrichment of the putative beneficial taxon unclassified [Eubacterium]_coprostanoligenes_group. Targeted metabolomics revealed that CM restored HFD-suppressed levels of colonic short-chain fatty acids (SCFAs), including acetic, butyric, and propionic acids. Untargeted liver metabolomics revealed that CM remodeled the hepatic metabolome, reversing HFD-induced elevations in sphingolipids [sphingosine, SM(d18:0/16:1(9Z))], and modulating lipid, glutathione metabolisms, and oxidative stress pathway. Liver transcriptomic analysis indicated that CM partially reversed HFD-induced gene expression changes, particularly downregulating genes involved in arachidonic acid metabolism (Cyp4a family), fatty acid elongation (Acot family), and glycerolipid metabolism (Aldh3a2, Mgll, Mogat1), while modulating bile secretion genes. Spearman correlation analyses further revealed significant associations between CM-modulated gut microbial genera (notably unclassified [Eubacterium]_coprostanoligenes_group, Faecalitalea, and Escherichia-Shigella) and obesity-related parameters, SCFA levels, hepatic metabolites, and lipid metabolism-related gene expression. These findings suggest that CM attenuates HFD-induced obesity and associated metabolic disturbances in association with gut microbiota modulation, enhanced SCFA production, and remodeling of hepatic lipid metabolism involving the gut-liver axis, pointing to CM as a potential dietary intervention for obesity management.