Apigenin Alleviates Dyslipidemia and Hepatic Steatosis in Obese Mice

by | Mar 4, 2019 | 2016, Flavonoids, Fruits and Vegetables, Obesity

Written by Angeline A. De Leon, Staff Writer. A sixteen-week supplementation of apigenin (0.005%, w/w) significantly improved dyslipidemia and hepatic steatosis in the high-fat diet fed mice.

fruits and vegetablesInflammation is known to play a major role in obesity and obesity-related metabolic diseases 1. Sustained systemic inflammation has been found to strongly increase risk of development of cardiometabolic disorders, such as diabetes and obesity 2. Thus, strategies for treating obesity have focused on the use of anti-inflammatory agents 3. Apigenin is a plant-derived flavonoid, abundant in many fruits and vegetables, such as parsley, onions, and grapefruit, which shows anti-inflammatory properties and the ability to protect against cardiovascular disease and cancer 4. More recent work has uncovered additional anti-obesity and anti-diabetic effects associated with the phytochemical compound apigenin that shows the ability to suppress adipogenesis (the process by which adipocytes, fat cells, become formed) 5, improve glucose tolerance and hepatic lipid metabolism in mice fed a high-fat diet (HFD) 6, and also lower food intake and weight in obese mice 7. Less clear, however, are the long-term supplementary effects of apigenin on obesity and other markers of metabolic health. To this end, a 2016 investigation 8 published in Nutrients sought to elucidate the effects of apigenin on adiposity, insulin resistance, dyslipidemia (elevation of fat in the blood), and nonalcoholic fatty liver disease (NAFLD, linked to obesity 9 and characterized by hepatic steatosis (excessive fat accumulation in the liver) in HFD-induced obese mice.

A group of 24 four-week old mice were randomly divided into two groups: one was fed a HFD (with 40% of energy coming from fat, 17% from protein and 43% from carbohydrates); the other was fed a HFD with 0.0005% (w/w) apigenin for 16 weeks. Every 2 weeks, fasting blood samples were taken from the tail vein, and fasting blood glucose, plasma insulin levels, and homeostatic index of insulin resistance (HOMA-IR) were measured. Plasma adipocytokines (leptin; tumor necrosis factor-α, TNF- α; interleukin-6, IL-6), lipids (triglycerides, total cholesterol), apolipoproteins (ApoA1, ApoB), and aminotransferase (alanine aminotransferase, ALT; aspartate aminotransferase, AST; indicator of liver cell injury) levels were also measured using enzymatic kits. Following anesthetization of mice, liver and adipose tissue were removed and analyzed for hepatic enzyme activity.

At the end of 16 weeks, apigenin was not shown to alter food intake, body weight gain, or fat accumulation. However, after two weeks, fasting blood glucose (p < 0.001), plasma insulin (p < 0.05), and HOMA-IR (p < 0.05) were significantly reduced by apigenin administration. Apigenin also lowered hepatic glucose metabolism-related enzyme activities (phosphoenolpyruvate carboxykinase, PEPCK, p < 0.001; mitochondrial glucose-6-phosphatase, G6Pase, p < 0.001) as well as plasma levels of pro-inflammatory mediators (MCP-1, IFN- γ, TNF- α, and IL-6; p < 0.05 for all). Apigenin was found to significantly reduce plasma free fatty acid levels (p < 0.05) and plasma total cholesterol levels (p < 0.05), as well as plasma apoB levels and the apoB/apoA1 ratio (p < 0.05). Finally, supplementation with apigenin was associated with reduced liver weight (p < 0.05) and lower plasma ALT and AST levels (p < 0.05 for both), along with diminished activity of hepatic enzymes controlling synthesis of triglyceride and cholesterol ester (microsomal phosphatidate phosphohydrolase, PAP; acyl CoA cholesterol acyltransferase, ACAT) (p < 0.001 for both).

Findings from the study indicate that although apigenin was not associated with alterations in body weight or fat accumulation, potentially due to the relatively low dose used in the trial, the phytochemical compound did improve markers of metabolic health, including fasting blood glucose, insulin, and HOMA-IR. In addition, supplementation with apigenin resulted in reduced activity of hepatic enzymes involved in gluconeogenesis (PEPCK and G6Pase 10 and the synthesis of triglycerides and cholesterol esters (PAP and ACA), as well as lower levels of pro-inflammatory cytokines and improved lipid profile. Based on findings, incorporation of apigenin in a high-fat diet appears to help ameliorate dyslipidemia, hepatic steatosis, and insulin resistance. Thus, researchers suggest that apigenin may offer protective effects against obesity and related metabolic disturbances. It would be valuable to translate findings in a human model of NAFLD as well as to conduct further studies to determine the dose-response relationship of apigenin supplementation.

Source: Jung, Un, Yun-Young Cho, and Myung-Sook Choi. “Apigenin ameliorates dyslipidemia, hepatic steatosis and insulin resistance by modulating metabolic and transcriptional profiles in the liver of high-fat diet-induced obese mice.” Nutrients 8, no. 5 (2016): 305.

© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).

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 Posted March 4, 2019.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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