A dietary anthocyanin cyanidin-3-O-glucoside binds to PPARs to regulate glucose metabolism and insulin sensitivity in mice

Abstract

We demonstrate the mechanism by which C3G, a major dietary anthocyanin, regulates energy metabolism and insulin sensitivity. Oral administration of C3G reduced hepatic and plasma triglyceride levels, adiposity, and improved glucose tolerance in mice fed high-fat diet. Hepatic metabolomic analysis revealed that C3G shifted metabolite profiles towards fatty acid oxidation and ketogenesis. C3G increased glucose uptake in HepG2 cells and C2C12 myotubes and induced the rate of hepatic fatty acid oxidation. C3G directly interacted with and activated PPARs, with the highest affinity for PPARα. The ability of C3G to reduce plasma and hepatic triglycerides, glucose tolerance, and adiposity and to induce oxygen consumption and energy expenditure was abrogated in PPARα-deficient mice, suggesting that PPARα is the major target for C3G. These findings demonstrate that the dietary anthocyanin C3G activates PPARs, a master regulators of energy metabolism. C3G is an agonistic ligand of PPARs and stimulates fuel preference to fat.

A review of the lipolytic effects and the reduction of abdominal fat from bioactive compounds and moro orange extracts

“…These compounds upregulate the expression of lipolytic genes in the liver by regulating enzymes involved in β-oxidation such as peroxisome proliferator activated receptor (PPAR) α and acyl-CoA oxidase while inhibiting the expression of lipogenic genes such as Liver X Receptor (LXR) and Fatty Acid Synthase (FAS) substantially improving fat accumulation in liver and the reduction of blood levels of triacylglycerols ( Figure 3 ) ( Nakajima, 2016 ).

Figure 3 Schematic model of the pharmacological action mechanisms of Citrus sinensis (Adapted from Jia et al., 2020 ; Wang et al., 2019 ). Ferulic acid and Ascorbic acid act mainly by neutralizing reactive oxygen species.

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“… Schematic model of the pharmacological action mechanisms of Citrus sinensis (Adapted from Jia et al., 2020 ; Wang et al., 2019 ). Ferulic acid and Ascorbic acid act mainly by neutralizing reactive oxygen species.…”

“…Anthocyanidins and their glycosides, anthocyanins, are essential water-soluble pigments that contribute to the coloring of various flowers, seeds, fruits and plants. They are phytochemicals belonging to a class of flavonoids that have recently demonstrated several promising biological activities in human health including prevents dyslipidaemia, type 2 diabetes, neurodegeneration, cardiovascular disease, liver diseases and cancer ( Jia et al., 2020 ; Lv et al., 2015 ; Rupasinghe et al., 2016 ). Anthocyanins are found naturally in a variety of dark-colored foods such as apple, apricot, blackberry, blackcurrant, blueberry, cranberry, grape, purple carrot, raspberry, strawberry and some other citrus fruits ( Zhang et al., 2019 ; Sivamaruthi et al., 2020 ).…”

“…Interestingly, C3G is a molecular structure more stable than its aglycone cyanidin (CYN) form in aqueous solution; therefore, C3G is more bioavailable and more active than the cyanidin (CYN) form in human tissues. However, the mechanisms of action and the target genes of C3G still remain unclear ( Jia et al., 2020 ).…”

Anti-Inflammatory and Anti-Diabetic Effect of Black Soybean Anthocyanins: Data from a Dual Cooperative Cellular System

“…Thiazolidinediones are PPARγ agonists that have been used for the treatment of T2DM. Anthocyanins have been shown to activate PPARγ by functioning as agonistic ligands [ 39 ]. In this study, BSAn increased the expression of PPARγ that was suppressed by coculture with macrophages.…”