Naringenin Prevents Dyslipidemia, Apolipoprotein B Overproduction, and Hyperinsulinemia in LDL Receptor–Null Mice With Diet-Induced Insulin Resistance

Abstract

OBJECTIVEThe global epidemic of metabolic syndrome and its complications demands rapid evaluation of new and accessible interventions. Insulin resistance is the central biochemical disturbance in the metabolic syndrome. The citrus-derived flavonoid, naringenin, has lipid-lowering properties and inhibits VLDL secretion from cultured hepatocytes in a manner resembling insulin. We evaluated whether naringenin regulates lipoprotein production and insulin sensitivity in the context of insulin resistance in vivo.RESEARCH DESIGN AND METHODSLDL receptor–null (Ldlr−/−) mice fed a high-fat (Western) diet (42% calories from fat and 0.05% cholesterol) become dyslipidemic, insulin and glucose intolerant, and obese. Four groups of mice (standard diet, Western, and Western plus 1% or 3% wt/wt naringenin) were fed ad libitum for 4 weeks. VLDL production and parameters of insulin and glucose tolerance were determined.RESULTSWe report that naringenin treatment of Ldlr−/− mice fed a Western diet corrected VLDL overproduction, ameliorated hepatic steatosis, and attenuated dyslipidemia without affecting caloric intake or fat absorption. Naringenin 1) increased hepatic fatty acid oxidation through a peroxisome proliferator–activated receptor (PPAR) γ coactivator 1α/PPARα-mediated transcription program; 2) prevented sterol regulatory element–binding protein 1c–mediated lipogenesis in both liver and muscle by reducing fasting hyperinsulinemia; 3) decreased hepatic cholesterol and cholesterol ester synthesis; 4) reduced both VLDL-derived and endogenously synthesized fatty acids, preventing muscle triglyceride accumulation; and 5) improved overall insulin sensitivity and glucose tolerance.CONCLUSIONSThus, naringenin, through its correction of many of the metabolic disturbances linked to insulin resistance, represents a promising therapeutic approach for metabolic syndrome.

A Review of Natural Stimulant and Non‐stimulant Thermogenic Agents

“…In animal models, citrus flavonoid supplements prevent hepatic steatosis, dyslipidemia, and insulin sensitivity primarily through inhibition of hepatic fatty acid synthesis and increased fatty acid oxidation (Mulvihill et al , 2009). Citrus flavonoids blunt the inflammatory response in metabolically important tissues including liver and adipose tissue, which may prevent obesity (Alam et al , 2014; Parhiz et al , 2015).…”

Hypo-Cholesterolemic and Hypoglycemic Effects of Orange Albedo Powder (Citrus Aurantium L.) on Male Albino Rats

“…Among the few mechanistic studies on hypoglycemic effects of flavonoids, it has been shown that naringenin, similarly to other polyphenols significantly increased AMP kinase (AMPK) activity and glucose uptake in muscle cells and liver (38,39). The hypoglycaemic activity of naringenin in vivo can be more complex and may depend on multilevel effects on lipid metabolism that lead to increased insulin sensitivity and glucose tolerance as shown in animal models of metabolic syndrome (40).…”

Regulation of plasma lipid profile by lactobacillus fermentum (probiotic strain ME-3 DSM14241) in a randomised controlled trial of clinically healthy adults

“…The baseline values represent the numbers of BL1 both for PG and CG compounds from various large complexes formed from foodstuffs; some of these bioactive compounds could affect the blood lipid profile [37]. For example, some aglycones derived from food-borne glycosides had positive effects on the blood lipid profile by increasing hepatic fatty acid oxidation and inhibiting cholesterol synthesis [42][43][44].…”