Proanthocyanidins Ameliorated Deficits of Lipid Metabolism in Type 2 Diabetes Mellitus Via Inhibiting Adipogenesis and Improving Mitochondrial Function

Abstract

Proanthocyanidins are the major active compounds extracted from Iris lactea Pall. var. Chinensis (Fisch.) Koidz (I. lactea). Proanthocyanidins exhibit a variety of pharmacological activities such as anti-oxidation, anti-inflammation, anti-tumor, and lowering blood lipids. However, the underlying mechanism of its regulating effect on lipid metabolism in diabetic conditions remains unclear. The present study investigated the effects of I. lactea-derived proanthocyanidins on lipid metabolism in mice of type 2 diabetes mellitus (T2DM). Results demonstrated a beneficial effect of total proanthocyanidins on dysregulated lipid metabolism and hepatic steatosis in high-fat-diet/streptozocin (STZ)-induced T2DM. To identify the mechanisms, six flavan-3-ols were isolated from proanthocyanidins of I. lacteal and their effects on adipogenesis and dexamethasone (Dex)-induced mitochondrial dysfunctions in 3T3-L1 adipocytes were determined. In vitro studies showed flavan-3-ols inhibited adipogenesis and restored mitochondrial function after Dex-induced insulin resistance, being suggested by increased mitochondrial membrane potential, intracellular ATP contents, mitochondrial mass and mitochondrial biogenesis, and reduced reactive oxygen species. Among the six flavan-3-ols, procyanidin B3 and procyanidin B1 exhibited the strongest effects. Our study suggests potential of proanthocyanidins as therapeutic target for diabetes.

Grape-Seed Proanthocyanidin Extract Reverts Obesity-Related Metabolic Derangements in Aged Female Rats

“…Standardized methods, doses, and times of administration are therefore required. Apart from body weight modulation, several beneficial effects of PACs have been demonstrated in young experimental animals, including (1) a decrease in fatty acid synthesis and fat uptake and an increase in energy expenditure in skeletal muscle and the liver [ 13 , 15 ]; (2) a modulation of the neuropeptides involved in food intake and satiety [ 13 ]; (3) an inhibition of digestive enzymes, mainly amylase and lipase, which leads to a reduction in lipid and glucose absorption from the gut [ 12 , 13 ]; (4) an antioxidant beneficial effect on inflammatory processes through reduction in the activity of antioxidant enzymes, such as catalase or superoxide dismutase (SOD) [ 12 ]; and (5) hypolipidemic and hypotriglyceridemic effects that lead to an improvement in lipid metabolism and the attenuation of hepatic steatosis in mice fed a high-fat diet [ 16 ] and rabbits fed a high-fat, high-cholesterol diet [ 17 ].…”

Intervention of Gastrodin in Type 2 Diabetes Mellitus and Its Mechanism

“…The aqueous extract of Gynura divaricata (L.) improving glucose and lipid metabolism was elucidated by establishing an obesity animal model induced by high-fat diet in combination with streptozocin and an insulin-resistant HepG2 cell model induced by dexamethasone ( Li J et al, 2018 ). A beneficial effect of total proanthocyanidins on dysregulated lipid metabolism was demonstrated in high-fat-diet/STZ-induced T2DM mice, and the effects of six flavan-3-ols on adipogenesis and Dex-induced mitochondrial dysfunctions in 3T3-L1 adipocytes were determined to identify the mechanisms ( Tie et al, 2020 ). The HepG2 cells induced with insulin resistance by dexamethasone, together with type 2 diabetes mellitus (T2DM) model rats induced by feeding a high-fat diet for 8 weeks and injecting intraperitoneally with 30 mg/kg STZ, were used to investigate the effects of cajanonic acid A on the regulatory mechanisms of glucose and lipid metabolism ( Yang et al, 2018 ).…”

Association of m.5178C>A variant with serum lipid levels: a systematic review and meta-analysis

“…Notably, this hypothesis was verified by an emerging study conducted by Tian et al [12], in which, variant of m.5178C>A decreased ROS production and Caspase 3/7 activity, increased ATP production and membrane potential, and resistance to apoptosis. All these protective effects caused by this polymorphism demonstrated that variant of m.5178C>A was related to increased mitochondrial functions, which might benefit lipid metabolism [13][14][15][41][42][43][44].…”

“…Moreover, an emerging study [12] reported that m.5178C>A variant was associated with improved mitochondrial functions. Intriguingly, the improvement of mitochondrial functions was associated with ameliorated lipid metabolism [13][14][15]. When combined with the above speculation, a variant of m.5178C>A may benefit lipid profile by enhancing mitochondrial functions.…”