Carnosic Acid Modulates Increased Hepatic Lipogenesis and Adipocytes Differentiation in Ovariectomized Mice Fed Normal or High-Fat Diets.

Abstract

As postmenopausal women experience a rapid increase in cardiovascular disease (CVD) risk with an increase in abdominal fat, dietary interventions to reduce CVD risk have been emphasized. This study was aimed at investigating the effect of a high-fat diet (HFD) in combination with an ovariectomy on liver and adipose tissue fat metabolism. The efficacy of carnosic acid (CA) supplementation in the suppression of HFD- and ovariectomy-induced obesity was also evaluated. Ovariectomized (OVX) or sham-operated mice at eight weeks of age were fed with a normal diet (ND), HFD, ND and 0.02% CA, or HFD and 0.02% CA for 12 weeks. All of the animals were sacrificed at the age of 20 weeks. The blood and tissue markers of the lipogenesis and adipocyte differentiation were measured. As expected, ovariectomy decreased the uterus weight and serum 17β-estradiol concentration. The HFD and ovariectomy significantly contributed to increases in the body weight and total fat mass, which were effectively inhibited by CA supplementation. The circulating concentrations of insulin, leptin, and TG (triglyceride) were significantly higher in the HFD group, and the concentrations were two to five times higher in the OVX and HFD group compared with those of the ND group. The CA supplementation significantly lowered the insulin, leptin, and TG concentrations in the OVX and HFD mice. The hepatic protein expressions of pAMPK and pACC were up-regulated by CA supplementation in OVX mice fed either ND or HFD. The expressions of hepatic SREBP1c and FAS mRNA were the highest in the OVX and HFD group, which were suppressed by CA supplementation. The adipose tissue PPARγ, aP2, and lipoprotein lipase (LPL) mRNA expressions were up-regulated by a HFD or ovariectomy, while they were significantly reduced in the mice fed a CA supplemented diet. The TNF-α and IL-6 mRNA levels in the adipose tissue were decreased by providing CA in the OVX groups. These results suggest that HFD and ovariectomy independently contribute to body fat accumulation, and CA effectively alleviated the ovariectomy-induced increases in lipogenesis and adipocyte differentiation. Further human trials are required in order to evaluate the efficacy of rosemary-derive CA as natural anti-adipogenic compounds, especially in postmenopausal women.