Rutin‐activated adipose tissue thermogenesis is correlated with increased intestinal short‐chain fatty acid levels

Abstract

The activation of thermogenic programs in brown adipose tissue (BAT) and white adipose tissue (WAT) provides a promising approach to increasing energy expenditure during obesity and diabetes treatment. Although evidence has been found that rutin activates BAT against obesity and type 2 diabetes mellitus (T2DM), its potential mechanism is not completely understood. In this study, we focused on the potential modulating effect of rutin on short-chain fatty acids (SCFAs) and the thermogenesis of BAT and WAT, aiming to elucidate the molecular mechanism of rutin in the treatment of obesity and T2DM. The results showed that rutin could significantly reduce the body weight and fasting blood glucose, inhibit fat accumulation, relieve hepatic steatosis and ameliorate the disorder of glycolipid metabolism in db/db mice. Moreover, rutin also increased the expression of uncoupling protein 1 (Ucp1) and other thermogenic genes and proteins in BAT and inguinal WAT (IWAT), indicating that rutin activated BAT and induced browning of IWAT. Importantly, rutin markedly enhanced the concentration of SCFAs (acetate, propionate and butyrate) and SCFAproducing enzymes (acetate kinase (ACK), methylmalonyl-CoA decarboxylase (MMD) and butyryl-CoA (BUT)) in feces of db/db mice. In addition, rutin significantly increased the mRNA expression of monocarboxylate transporter 1 (Mct1), catabolic enzyme acyl-CoA medium-chain synthetase 3 (Acsm3), carnitine palmitoyl transferase 1α (Cpt-1α) and Cpt-1β genes in BAT and IWAT of db/db mice, which is conducive to inducing adipocyte thermogenesis. In summary, our findings revealed that rutin played a variety of regulatory roles in improving glucose and lipid metabolism disorders, reducing hepatic steatosis, inducing browning of IWAT and activating BAT, which has potential therapeutic significance for the treatment of obesity and T2DM.Mechanistically, rutin activates the thermogenesis of BAT and IWAT, which may be associated with increasing the concentration of SCFAs.

Mulberry Leaf Flavonoids Inhibit Liver Inflammation in Type 2 Diabetes Rats by Regulating TLR4/MyD88/NF-κB Signaling Pathway

“…In addition, the previous study of our research group found that rutin has potential therapeutic implications for the treatment of obesity and T2DM. Rutin decreased blood glucose in db/db mice, inhibited hepatic lipid accumulation, and improved glucose and lipid metabolism disorders; these pharmacological effects may be related to the promotion of the mRNA expression of the adipocyte thermogenic genes MCT1, MCT1, ACSM3, CPT-1 α , and CPT-1 β , activation of BAT and induction of browning of IWAT, and increasing the concentration of SCFA-producing enzymes, promoting the production of SCFA [ 19 ]. Isoquercetin has been shown to reduce serum ALT, AST, improve IR, increase HDL-C, reduce degeneration, necrosis, and apoptosis of liver tissue, and prevent liver damage caused by T2DM [ 20 ].…”

Diet-Related Changes of Short-Chain Fatty Acids in Blood and Feces in Obesity and Metabolic Syndrome

“…The study identification, selection, and inclusion process are summarized in Figure 2 . After eliminating duplicates, in total, 139 articles were included in this review, 112 from the first search term containing obesity [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , ...…”

“…In metabolic syndrome mice, caffeine and chlorogenic acid increased bAc, bProp, and bBu levels [ 156 ], while in the case of db/db mice (a type II diabetes and obese mutant mouse model), rutin (a citrus flavonoid) administration increased fSCFA [ 37 ]. Similarly, in monosodium glutamate (MSG)-induced obesity, fructo-oligosaccharides increased fAc, fProp, fBu, and bProp concentrations [ 99 ].…”

“…Diet, unequivocally, has a significant influence on both fecal and blood levels of SCFAs, as well as the relative abundance of Ac, Prop, and Bu [ 36 , 37 , 39 , 41 , 42 , 43 , 44 , 45 , 47 , 52 , 54 , 56 , 57 , 60 , 63 , 65 , 66 , 68 , 70 , 72 , 73 , 76 , 77 , 80 , 81 , 83 , 85 , 86 , 89 , 93 , 95 , 98 , 99 , 100 , 103 , 105 , 110 , 111 , 112 , 113 , 114 , 118 , 120 , 122 , 124 , 125 , 126 , 129 , 130 , 131 , 134 , 136 , 137 ,…”

An overview of traditional Chinese medicine affecting gut microbiota in obesity

“…In mice given a high-fat diet, Ren et al (96) discovered that Ganoderma lucidum polysaccharides efficiently lower blood lipid concentrations, regulate the abundance of gut bacteria and various critical pathways, and successfully relieve fat formation. According to Cheng et al (97), Rubin may greatly raise the amounts of SCFAs and SCFA-producing enzymes in the feces of obese mice, prevent fat accumulation, treat glucolipid metabolic problems, and cause obese animals to lose weight. Heat-treated adzuki bean protein hydrolysates can assist to prevent and treat obesity and its associated consequences, as well as increase the diversity of gut bacteria in mice fed a high-fat diet (98).…”