The flavonoid, naringenin, decreases adipose tissue mass and attenuates ovariectomy-associated metabolic disturbances in mice.
OBJECTIVE
Adverse metabolic changes associated with loss of ovarian function increase the risk of developing metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) in postmenopausal women. Naringenin improves metabolic disturbances in vitro and in vivo. In the present study, we tested the effects of naringenin on metabolic disturbances resulting from estrogen deficiency in ovariectomized mice.


METHODS
Ovariectomized C57BL/6 J female mice were fed a control diet (10% calories from fat) for 11 weeks. Mice either continued on the control diet (n = 9) or were switched to the control diet supplemented with 3% naringenin (n = 10) for the next 11 weeks. Energy expenditure was measured by indirect calorimetry and activity was monitored by infrared beam breaks. Intra-abdominal and subcutaneous adiposity was evaluated by magnetic resonance imaging (MRI). Blood biochemical measures of metabolic response included glucose, insulin, adipokines, and lipids. Lipid content in liver and muscle and expression of relevant genes in adipose tissue, liver, and muscle were quantified.


RESULTS
Ovariectomized mice fed naringenin exhibited lower fasting glucose and insulin levels compared to controls, with over 50% reduction of intra-abdominal and subcutaneous adiposity. Plasma leptin and leptin mRNA in adipose depots were also decreased in mice fed a naringenin diet. Monocyte chemoattractant protein-1 (MCP1/Ccl2) and interleukin 6 (IL-6/Il6) mRNA expression levels were significantly lower in perigonadal adipose tissue of naringenin-supplemented mice. We also observed that mice fed a naringenin diet had less hepatic lipid accumulation with corresponding alterations of hepatic gene expression associated with de novo lipogenesis, fatty acid oxidation, and gluconeogenesis.


CONCLUSIONS
Dietary naringenin attenuates many of the metabolic disturbances associated with ovariectomy in female mice.
Department of Human Sciences, Human Nutrition Program, College of Education and Human Ecology, The Ohio State University, Campbell Hall 302, 1787 Neil Avenue, Columbus, Ohio 43210 USA.
Jia-Yu
JY
Ke
Department of Human Sciences, Human Nutrition Program, College of Education and Human Ecology, The Ohio State University, Campbell Hall 302, 1787 Neil Avenue, Columbus, Ohio 43210 USA.
Kara L
KL
Kliewer
Department of Dairy Science, Faculty of Agriculture, Cairo University, Giza, Egypt.
Essam M
EM
Hamad
Department of Human Sciences, Human Nutrition Program, College of Education and Human Ecology, The Ohio State University, Campbell Hall 302, 1787 Neil Avenue, Columbus, Ohio 43210 USA.
Rachel M
RM
Cole
Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, Ohio USA.
Kimerly A
KA
Powell
Division of Biostatistics, College of Public Health, The Ohio State University, Columbus, Ohio USA.
Rebecca R
RR
Andridge
Department of Surgery, College of Medicine, The Ohio State University, Columbus, Ohio USA.
Shana R
SR
Straka
Department of Surgery, College of Medicine, The Ohio State University, Columbus, Ohio USA.
Lisa D
LD
Yee
Department of Human Sciences, Human Nutrition Program, College of Education and Human Ecology, The Ohio State University, Campbell Hall 302, 1787 Neil Avenue, Columbus, Ohio 43210 USA.
Martha A
MA
Belury
Adipose tissue inflammation; Fatty liver; Insulin sensitivity; Menopause; Naringenin; Obesity