Flavonoid-enriched extract from Hippophae rhamnoides seed reduces high fat diet induced obesity, hypertriglyceridemia, and hepatic triglyceride accumulation in C57BL/6 mice

Abstract

Context: Flavonoid-enriched extract from Hippophae rhamnoides L. (Elaeagnaceae) seed (FSH) has shown beneficial effects in anti-hypertension and lowering cholesterol level. However, evidence for its efficacy in treating obesity is limited.

Objective: We sought to determine if FSH can reduce body weight and regulate lipid metabolism disorder in high fat diet (HFD)-induced obese mouse model, and to investigate potential molecular targets involved.

Materials and methods: C57BL/6 mice were fed with HFD for 8 weeks to induce obesity. The modeled mice were divided into four groups and treated with vehicle, rosiglitazone (2 mg/kg), low (100 mg/kg) and high (300 mg/kg) dose of FSH, respectively. Normal control was also used. The treatments were administered orally for 9 weeks. We measured the effect of FSH on regulating body weight, various liver and serum parameters, and molecular targets that are key to lipid metabolism.

Results: FSH administration at 100 and 300 mg/kg significantly reduced body weight gain by 33.06 and 43.51%, respectively. Additionally, triglyceride concentration in serum and liver were decreased by 15.67 and 49.56%, individually, after FSH (300 mg/kg) treatment. Upon FSH (100 and 300 mg/kg) treatment, PPARα mRNA expression was upregulated in liver (1.24- and 1.42-fold) and in adipose tissue (1.66- and 1.72-fold). Furthermore, FSH downregulated PPARγ protein level both in liver and adipose tissue. Moreover, FSH inhibited macrophage infiltration into adipose tissues, and downregulated TNFα mRNA expression in adipose tissue (38.01-47.70%).

Conclusion: This effect was mediated via regulation of PPARγ and PPARα gene expression, and suppression of adipose tissue inflammation.

Keywords: Obese mice; PPARα; PPARγ; inflammation.

Figure 1.

Chromatograms of the standard sample (A) and the hydrolyzed sample (B) analyzed through HPLC. RuT: Rutin; MyR: Myricetin; QuE: Quercetin; Kam: kaempferol; Iso: Isorhamnetin.

Figure 2.

Effect of FSH on body weight and food intake in HFD-induced obese mice. (A) Body weight during the experiment. (B) Change of body weight between the 9th week and 17th week. (C) Average food intake per mouse was recorded at an interval of 3 d. (D) Abdominal adipose tissue. Values are expressed as mean ± S.E.M (n = 10). *p < 0.05, **p < 0.01, vs. the HFD group, respectively; ##p < 0.01, vs. the NC group.

Figure 3.

Effect of FSH on serum lipid profiles, blood glucose, hepatic TG, and OGTT. (A) Serum TG. (B) Serum TC. (C) Serum HDL-C/TC. (D) Fasting blood Glu. (E) Hepatic TG. (F) Blood glucose concentrations during an OGTT. (G) Area under the curve of blood glucose in OGTT. Values are expressed as mean ± S.E.M. (n = 10). *p < 0.05, **p < 0.01, vs. HFD group, respectively; ##p < 0.01, vs. NC group.

Figure 4.

Histological analysis of epididymial WAT and liver tissue. (A) Photomicrographs of epididymal WAT stained with HE (100×). (B) Photomicrographs of liver tissues stained with HE (100×). (C) Adipocyte size (% control, n = 500; 100×). (D) Photomicrographs of epididymal white adipose tissues with F4/80 antibody. Values are expressed as mean ± S.E.M (n = 10). *p < 0.05, **p < 0.01, vs. HFD group, respectively; ##p < 0.01, vs. NC group.

Figure 5.

Effects of FSH on mRNA expression in the liver (A) and epididymal WAT (B) of HFD-induced obese mice. Values are expressed as mean ± S.E.M (n = 6). *p < 0.05, **p < 0.01, vs. HFD group, respectively; ##p < 0.01, vs. NC group.

Figure 6.

Effects of FSH on the protein expressions of PPARγ in liver (A) and epididymal WAT (B) of HFD-induced obese mice.