Probiotics alleviate adipose inflammation in high-fat diet–induced obesity by restoring adipose invariant natural killer T cells

Abstract

ObjectiveInvariant natural killer T (iNKT) cells, which are depleted in obese individuals, play important roles in preventing diet-induced obesity and associated disorders. Probiotic supplementation can alter the gut microbiota and immunomodulation in obesity. However, it remains unclear whether probiotics can affect visceral adipose iNKT cells. The aim of this study was to analyze the effects of probiotics on adipose iNKT cells in mice with high-fat diet (HFD)-induced obesity and to assess the immunomodulatory function of probiotics and their role in obesity, glucose tolerance, lipid metabolism, insulin resistance, and adipose inflammation. MethodsWildtype (WT) male C57BL/6 mice and CD1d knockout mice were fed an HFD or a normal-fat diet. Some mice received active or heat-sacrificed VSL#3 probiotics. Preventative VSL#3 therapy was also administered to HFD mice. Body weight, metabolic parameters, expression of genes encoding adipose inflammatory factors (interleukin [IL]-4, IL-10, tumor necrosis factor-α, interferon-γ, and IL-6), adipose iNKT cell frequency, and subphenotype were evaluated. ResultsHFD induced more severe obesity in CD1dKO mice than in WT mice. VSL#3 intervention significantly improved HFD-induced weight gain, adipose iNKT cell depletion, and metabolic and adipose inflammatory profiles in WT mice, but not in CD1dKO mice. Preventative VSL#3 treatment improved HFD-induced obesity and metabolic parameters, and elevated total adipose iNKT and IL-4+ iNKT cell frequencies. ConclusionsProbiotic intervention alleviated weight gain, improved metabolic parameters, and reduced adipose inflammation in HFD-induced obesity. These effects seem to depend on the restoration of visceral adipose iNKT cells. These findings have potential implications for the management of obesity-related diseases.