Anti-obesity and anti-inflammatory effects of high hydrostatic pressure extract of mulberry leaves in high-fat diet-induced obese rats

Abstract

Obesity is associated with a state of chronically low-grade inflammation. The specific aim of this study was to investigate the anti-obesity and anti-inflammatory effect of high hydrostatic pressure extract of mulberry leaves. Three-week-old male Sprague-Dawley rats were randomly divided into four groups based on the diet: normal diet (NOR), high-fat diet (HF, 45% kcal fat), HF supplemented with 0.4% high hydrostatic pressure extract of mulberry leaves (PL), and HF supplemented with 0.8% high hydrostatic pressure extract of mulberry leaves (PH). After 14 weeks of experiment, the body weight, white adipose tissue mass, and adipocyte sizes of the PH group were lower than those of the HF group (P < 0.05). In the PH group, serum concentrations of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were lower, while the serum high- density lipoprotein cholesterol (HDL-C) concentration was higher than those in the HF group (P < 0.01). Fecal TG and TC excretion were greater in the PH group relative to those in the HF group (P < 0.05). In addition, the numbers of muscle mitochondria were increased in PL and PH group compared to the HF group. PH significantly down-regulated mRNA levels of adipogenic genes such as peroxisome proliferator activated receptor gamma (PPAR-γ), sterol regulatory element binding protein 1-c (SREBP1-c), and adipocyte protein 2 (aP2), compared to the HF group. (P < 0.05) IHC staining showed a decrease of the macrophage marker, F4/80, in white adipose tissue (WAT) of PH group, compared to the HF group. Moreover, mRNA levels of inflammatory genes such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and monocyte chemoattractant protein 1 (MCP1) were significantly down-regulated in the PH group, compared to the HF group (P < 0.01). The advantage of high hydrostatic pressure extract of mulberry leaves is supposed mainly attributed to polyphenols such as caffeic acid, rutin, and quercetin contained in mulberry leaves. These results suggest that high hydrostatic pressure extract of mulberry leaves could be used as nutraceutical to prevent obesity and obesity-induced inflammation.;비만은 만성적인 염증 상태를 야기한다. 본 연구는 뽕잎 고압추출물의 항비만과 항염증 효과를 연구하고자 수행되었다. 3주령의 수컷 SD rat을 식이에 따라 네 개의 군으로 나누어 (저지방 식이를 먹인 LF군, 45% 고지방 식이를 먹인 HF군, 고지방 식이에 0.4% 뽕잎 고압추출물이 추가된 PL군, 고지방 식이에 0.8% 뽕잎 고압추출물이 추가된 PH군) 14주 동안 섭취하도록 하였다. 고용량의 뽕잎고압추출물을 먹은 PH군에서 HF군에 비해 체중과 백색지방 무게가 유의적으로 감소하였으며 (P < 0.05), 지방구의 크기 또한 줄어들었다. 그리고 PH군에서 먹은 군에서 혈중 TG, TC, LDL-C 농도가 감소하였으며, HDL-C 농도가 증가하였다 (P < 0.05). 또한, PH군에서 변 TG와 TC의 배출양이 증가하였으며, 근육 미토콘드리아의 크기와 숫자 또한 증가하였다. PPAR-γ, SREBP1-c, aP2와 같은 지방합성 유전자의 발현이 PH 군에서 유의적으로 감소하였다 (P < 0.05). F4/80 면역염색을 하여 PL, PH군에서 대식세포 침륜도가 감소한 것을 확인하였으며, TNF-α, IL-6, MCP1과 같은 염증 관련 유전자의 발현 또한 PH군에서 유의적으로 감소하였다 (P < 0.05). 이러한 뽕잎고압추출물의 효과는 뽕잎 안에 다량 함유되어있다고 알려진 rutin, quercetin, caffeic acid 와 같은 polyphenol의 작용 때문인 것으로 추측된다. 따라서, 위 결과들을 종합하여 볼 때, 뽕잎고압추출물은 비만과 염증을 예방하는 데에 사용될 수 있는 기능성 소재일 것으로 사료된다.