Insect chitosan derived from Hermetia illucens larvae suppresses adipogenic signaling and promotes the restoration of gut microbiome balance.

Chitosan, the deacetylated form of chitin, is considered a valuable source of compounds in the feed and food industries. However, the impact of Hermetia illucens larvae chitosan (HCS) with specific physicochemical characteristics on obesity mediated by lipid accumulation and microbiome dysbiosis has not been fully elucidated. We purified HCS with a low molecular weight (84 kDa), low crystallinity, and a high deacetylation rate, characterizing it through several analytical techniques, including gel permeation chromatography, FT-IR, 1H NMR, FE-SEM, and XRD analysis. HCS effectively inhibited the differentiation of 3T3-L1 preadipocytes by suppressing the production of reactive oxygen species. The adipogenic signaling of preadipocytes, mediated by the phosphorylation of mTOR and PPARγ, which are essential for the expression of fatty acid synthase, was attenuated by HCS. In mouse models fed high-fat diets, the oral administration of HCS prevented changes in white adipose tissue and liver weight and reduced plasma levels of total cholesterol. Additionally, the analysis of the microbiota using 16S rRNA revealed that HCS improved dysbiosis by modulating the composition and abundance of specific bacterial genera, including F. rodentium, L. gasseri, L. reuteri, and L. murinus. These findings highlight the potential of HCS as a candidate for the treatment of obesity-related metabolic diseases.