Molecular Mechanisms of the Anti-Obesity and Anti-Diabetic Properties of Flavonoids - PubMed (original) (raw)
Review
Molecular Mechanisms of the Anti-Obesity and Anti-Diabetic Properties of Flavonoids
Mohammed Kawser Hossain et al. Int J Mol Sci. 2016.
Abstract
Obesity and diabetes are the most prevailing health concerns worldwide and their incidence is increasing at a high rate, resulting in enormous social costs. Obesity is a complex disease commonly accompanied by insulin resistance and increases in oxidative stress and inflammatory marker expression, leading to augmented fat mass in the body. Diabetes mellitus (DM) is a metabolic disorder characterized by the destruction of pancreatic β cells or diminished insulin secretion and action insulin. Obesity causes the development of metabolic disorders such as DM, hypertension, cardiovascular diseases, and inflammation-based pathologies. Flavonoids are the secondary metabolites of plants and have 15-carbon skeleton structures containing two phenyl rings and a heterocyclic ring. More than 5000 naturally occurring flavonoids have been reported from various plants and have been found to possess many beneficial effects with advantages over chemical treatments. A number of studies have demonstrated the potential health benefits of natural flavonoids in treating obesity and DM, and show increased bioavailability and action on multiple molecular targets. This review summarizes the current progress in our understanding of the anti-obesity and anti-diabetic potential of natural flavonoids and their molecular mechanisms for preventing and/or treating obesity and diabetes.
Keywords: anti-diabetic; anti-obesity; diabetes; flavonoids; molecular mechanism; obesity.
Figures
Figure 1
Schematic diagram of the link between obesity and diabetes as well as their effects in skeletal muscle, liver, and pancreas for stimulating different inflammatory cytokines, metabolic enzymes, and signaling pathways. Nutrition, physical inactivity, environmental factors, and genetic susceptibility cause obesity and fat deposition that initiates chronic low-grade inflammation to release MCP-1, leptin, resistin, TNF-α, adiponectin, IL-6, and IL-1β. Chronic inflammation leads to increased secretion of FFA from the liver, skeletal muscles, and pancreas. Increased FFA reduces the expression of IRS-1 and PI3K-AKT in the liver and skeletal muscles and increased JNK expression in the pancreas, ultimately causing insulin resistance in the liver and muscle and increasing apoptosis in the pancreas. Insulin resistance causes glucose production increase and glucose uptake decrease, and insulin secretion decreases because of increased apoptosis of pancreatic β cells. MCP-1: monocyte-chemo-attractant protein-1 [19]; TNF-α: tumor necrosis factor α [21]; IL-6: interleukin-6 [19]; IL-1β: interleukin 1 β [19]; FFA: free fatty acid [23]; IRS1: insulin receptor substrate 1 [24,25]; PI3K: phosphatidylinositol 3-kinase [24,25]; AKT: serine/threonine kinase [24,25]; JNK: c-Jun N-terminal kinase [26] FA: fatty acid [23]; IGT: impaired glucose tolerance [23]. (↓) Decrease, (↑) Increase.
Figure 2
Classification and example of flavonoids and their chemical structures. Flavonoids are classified into six groups, including flavonol, flavanone, isoflavone, flavone, flavan-3-ols, and anthocyanin. Chemical structures of each of the six classes of flavonoids are shown as examples, including isorhamnetin for flavonol, naringin for flavanone, daizein for isoflavone, apigenin for flavone, catechin for flavov-3-ols, and cyanidin for anthocyanins.
Figure 3
Schematic presentation of molecular functions of different flavonoids with anti-obesity and anti-diabetic effects. Obesity and diabetes stimulate increased or decreased production of inflammatory cytokines, expression of different metabolites, and intracellular cell signaling. Flavonoids showed anti-obesity and anti-diabetic effects by activating or inhibiting different cytokines, enzymes, and metabolites to prevent inflammation, oxidative stress, and metabolism to protect against obesity and diabetes. MCP-1: monocyte-chemo-attractant protein-1; TNF-α: tumor necrosis factor alpha; IL-6: interleukin-6; IL-1β: interleukin 1 beta; FFA: free fatty acid, IRS1: insulin receptor substrate 1; PI3K: phosphatidylinositol 3-kinase; AKT: serine/threonine kinase; FA: fatty acid; IGT: impaired glucose tolerance; PARP: poly(ADP-ribose) polymerase; BCl-2: B-cell lymphoma 2; Bax: Bcl-2-associated X protein; Bak: Bcl-2 homologous antagonist/killer; Caspase 3: cysteine-dependent aspartate-directed proteases 3; PPAR γ: peroxisomal proliferator-activated receptor gamma; SREBP1c: sterol regulatory element binding protein-1c; LPL: lipo protein lipase; AMPK: 5′ adenosine monophosphate-activated protein kinase; HOMA-IR: homeostatic model assessment for insulin resistance; HbA1c: hemoglobin A1c; GLUT4: glucose transporter 4; G6PDH: glucose-6-phosphate dehydrogenase; HMG-CoA: 3-hydroxy-3-methylglutaryl-coenzyme; ACAT: acyl CoA: cholesterol acyltransferase; G6pase: glucose-6-phosphatase; cAMP: cyclic adenosine monophosphate; PKA: protein kinase A. (↓) Decrease, (↑) Increase.
Figure 4
Graphical presentation of anti-obesity and anti-diabetes effect of flavonoids and their subsequent effects in skeletal muscles, liver, and pancreas to induce glucose uptake, increase insulin secretion, and reduce oxidative damage and lipid accumulation. Research on the molecular action of flavonoids would help in developing new strategies for discovery of safe and specific anti-obesity and anti-diabetic drugs. CHO: Carbohydrate. (↑) Increase, (↓) Decrease.
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