Conjugated linoleic acid (CLA) may prevent the development of
obesity and metabolic disorders. However, the effects of CLA on
inflammation and
glucose metabolism are controversial. The underlying mechanisms governing the gut microbiota and sexual dimorphisms have also not been elucidated. The present study assessed the effect of CLA on
glucose and lipid metabolism in established
obesity and examined the mechanism of action based on gut microbiota. Four-week-old C57BL/6J mice were fed a high-fat diet (HFD) for 10 weeks to induce
obesity. The diet-induced obese (DIO) mice were fed an HFD supplemented with mixed CLA (50% cis-9, trans-11 isomer and 50% trans-10, cis-12 isomers, 0.2% wt/wt) for 15 weeks. CLA supplementation remarkably reversed
body weight in both sexes. CLA favored anti-inflammatory microbiota in male mice, mediating increased
short-chain fatty acids and decreased
lipopolysaccharide (LPS) production, which alleviated global
inflammation and improved
insulin sensitivity via inhibition of the TLR4-NF-κB pathway in adipose tissue. CLA promoted the growth of
hydrogen sulfide-producing Desulfovibrio and the release of LPS in female mice, which aggravated adipose
inflammation and
insulin resistance. Although CLA impaired
glucose metabolism in females, brown adipose tissue was significantly activated with browning of white adipose tissue in both sexes, which led to enhanced energy expenditure.
Fecal transplantation from CLA-treated mice to DIO mice mimicked the sex-dependent phenotype. In conclusion, CLA decreased
body weight and increased energy expenditure but sex-dependently modulated
insulin resistance via the gut-adipose axis.