Dihydromyricetin Improves High‐Fat Diet‐Induced Hyperglycemia through ILC3 Activation via a SIRT3‐Dependent Mechanism

Abstract

Scope: Previous studies indicate that dihydromyricetin (DHM) effectively improved glucose homeostasis and alleviated insulin resistance in population-intervened trials, yet the underlying mechanism remains obscure. Methods and results: Wild-type male mice and recombinase activating gene 1(Rag1) -/mice (lacking adaptive immunity lymphocytes) are fed with control, high-fat diet (HFD), or HFD+DHM diets for 8 weeks. DHM effectively protects HFD feeding mice against hyperglycemia by promoting group 3 innate lymphoid cells (ILC3s) cells proliferation and interleukin 22 (IL-22) production. Furthermore, IL-22 secretion induced by DHM increases the expression levels of the tight junction (TJs) molecules to protect the intestinal barrier integrity, thereby decreasing the level of lipopolysaccharides (LPS), an endotoxin that is involved in the regulation of chronic tissue inflammation and insulin resistance. In addition, silent mating-type information regulation 2 homolog 3 (SIRT3) deficiency results in more serious obesity and intestinal barrier damage following HFD feeding and abolished DHM-mediated increase in IL-22 expression levels of ILC3 cells in SIRT3 knockout (SIRT3KO) mice. DHM reduces metabolic stress and enhances mitochondrial respiratory capacity to promote cell proliferation and IL-22 secretion by activating SIRT3 in ILC3 cells Conclusions: DHM improves IL-22 production of ILC3 cells and subsequently inhibits intestinal barrier dysfunction to alleviate hyperglycemia partially mediated by SIRT3.

Lactobacillus paracaseiinfluences the gut-microbiota-targeted metabolic modulation of the immune status of diarrheal mice

“…LC-MS was used to investigate the possible correlation between the effect of L. paracasei and metabolism; the occurrence of diarrhea was related to intesti-nal microflora disruption. In this study, there are some antiinflammatory metabolites, such as dihydromyricetin, [63][64][65] and pinocembrin, [66][67][68][69] which were increased in the PE group, whereas dihydrokaempferol, 70,71 pinocembrin, dihydromyricetin, and rimexolone, which can inhibit CD4 + T cells, 72 were reduced in the CIP group. The results suggest that L. paracasei can promote the production of anti-inflammatory substances.…”

Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H2O2 pathway and alleviating diabetic retinopathy

“…Zhou et al. [ 56 ] have demonstrated that DMY can regulate a sirtuin 3-dependent mechanism to reduce metabolic stress, enhance mitochondrial respiration, and alleviate hyperglycemia. Furthermore, Le et al.…”

Dihydromyricetin Protects Intestinal Barrier Integrity by Promoting IL-22 Expression in ILC3s through the AMPK/SIRT3/STAT3 Signaling Pathway

“…The small intestine collected from mice was washed with precooled PBS to remove feces and then cut into segments. Immune cells on lamina propria obtained from small intestinal tissues were resuspended in PBS for flow cytometry, according to our previous study [ 17 ].…”