Citrus flavonoid, naringenin, increases locomotor activity and reduces diacylglycerol accumulation in skeletal muscle of obese ovariectomized mice

Abstract

Scope Estrogen deficiency has been associated with central obesity, muscle loss, and metabolic syndrome in postmenopausal women. This study assessed naringenin accumulation in tissues and investigated the hypothesis that naringenin reverses diet-induced metabolic disturbances in obese ovariectomized mice. Methods and results In study 1, we measured naringenin concentrations in plasma, liver, perigonadal and subcutaneous adipose tissues, and muscle of ovariectomized C57BL/6J female mice after 11 weeks of naringenin supplementation. Naringenin accumulated 5–12 times more in mice fed a 3% naringenin diet than in mice fed a 1% naringenin diet. In study 2, ovariectomized mice were fed a high-fat diet (60 kcal% fat) for 11 weeks and half of the mice were then supplemented with 3% naringenin for another 11 weeks. Dietary naringenin suppressed weight gain, lowered hyperglycemia, and decreased intra-abdominal adiposity evaluated by magnetic resonance imaging. Naringenin-fed mice exhibited elevated locomotor activity monitored by infrared beam breaks, maintained muscle mass, and reduced muscle diacylglycerol content. Real-time PCR analysis in muscle revealed decreased mRNA level for genes involved in de novo lipogenesis, lipolysis, and triglyceride synthesis/storage. Conclusions Long-term 3% naringenin supplementation resulted in significant naringenin accumulation in plasma and tissues, associated with attenuated metabolic dysregulation and muscle loss in obese ovariectomized mice.

Citrus flavonoid naringenin reduces mammary tumor cell viability, adipose mass, and adipose inflammation in obese ovariectomized mice

“…The final tumor weight was not different among groups but strongly correlated with weight gain before tumor implantation, suggesting that weight loss induced by HN supplementation may play a role in tumor growth. Previously, in obese OVX mice fed a high‐fat diet with 3% naringenin exhibited decreased body weight without significant differences in cumulative food intake compared to the high‐fat group without naringenin . We noticed a similar reduction in caloric intake in the first 5 weeks, but the caloric intake recovered gradually so that after 11 weeks food intake was not significantly different from the HF group.…”

“…Previously, we found that naringenin acts in a manner similar to metformin to reduce hepatic glucose production, decrease cellular adenosine triphosphate (ATP) levels, and activate AMPK in hepatocytes . Naringenin also lowered blood glucose levels and adipose mass in lean and obese ovariectomized mice . Metformin is currently regarded as a promising target for breast cancer prevention and treatment.…”

“…Male mice fed a high-fat diet supplemented with naringenin showed suppression of diet-induced weight gain, adipose mass, and blood glucose and insulin levels [10]. We previously reported that naringenin exhibited similar effects on blood glucose levels and adipose mass in lean and obese ovariectomized (OVX) mice, a mouse model for human postmenopause [11,12]. Additionally, studies revealed that naringenin possesses antitumorigenic activity in various cancer cell lines and animal models [13][14][15][16][17][18].…”

Naringenin Supplementation to a Chow Diet Enhances Energy Expenditure and Fatty Acid Oxidation, and Reduces Adiposity in Lean, Pair‐Fed Ldlr−/− Mice

“…Purified naringenin was continuously supplemented to the purified rodent chow by weight (3%; wt/wt) fed ad libitum. A 3% oral dose was chosen based on previous studies in the laboratory and others . Naringenin (like most flavonoids) has relatively low bioavailability (3–6%), such that naringenin needs to be administered at a high enough doses to achieve physiologically relevant blood levels.…”

“…Naringenin is a citrus‐derived flavonoid that is found abundantly in grapefruits and tomatoes and exhibits a diverse range of biological functions such as anti‐cancer, anti‐inflammation, and anti‐atherosclerotic activities . It has been studied in humans and mice and although its bioavailability is low, it accumulates in the liver, with lesser amounts in adipose tissue, muscle, and plasma of mice fed naringenin . Therefore, the health benefits of grapefruit consumption may be due in part to the molecular effects of naringenin.…”