脂肪因子Omentin-1对代谢综合征小鼠的影响及可能机制
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摘要
探讨脂肪因子Omentin-1对代谢综合征((metabolic syndrome,MS)小鼠的影响及可能机制。选择6～8周龄SPF级雄性BALB/c小鼠,通过高脂高糖饮食建立MS模型,将小鼠随机分为模型组及治疗组。治疗组给予腹腔注射Omentin-1 [8μg/(kg·d)],模型组给予腹腔注射等量生理盐水。干预4周后,采用免疫组化、ELISA及Western blotting等方法评估Omentin-1治疗对MS小鼠糖、脂质代谢及系统性炎症的影响,并进一步分析Omentin-1对小鼠内脏脂肪组织炎症及过氧化物酶体增殖物激活受体γ(peroxisome proliferators-activated receptor-γ, PPAR-γ)信号的影响。研究发现治疗组小鼠空腹血糖(fasting blood-glucose,FBG)、甘油三酯(triglyceride,TG)及低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)水平均显著低于模型组(P<0.05),而高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)水平显著高于模型组(P<0.05)。治疗组小鼠外周血IL-8及TNF-α水平均显著低于模型组(P<0.05)。治疗组小鼠脂肪组织巨噬细胞浸润及IL-6水平均显著低于模型组(P<0.05),但IL-10水平显著高于模型组(P<0.05)。治疗组小鼠脂肪组织PPAR-γ及脂联素水平显著高于模型组(P<0.05)。这提示Omentin-1可有效改善MS小鼠系统性炎症及糖、脂质代谢,可能与激活脂肪组织PPAR-γ信号通路有关。
In order to investigate the effect of Omentin-1 on mouse metabolic syndrom(MS) and its possible mechanism, we selected 6-8 weeks old SPF male BALB/c mice and established a MS model through high-fat and high-sugar diet. The mice were divided into the model group and the treatment group. The treatment group was given intraperitoneal injection of Omentin-1[8 μg/(kg·d)], and the model group was given an equal amount of normal saline. After 4 weeks of intervention, immunohistochemistry, ELISA and Western blotting were performed to evaluate the effects of Omentin-1 treatment on glucose and lipid metabolism, and systemic inflammation. In addition, the effect on inflammation in the visceral fat tissue and on peroxisome proliferators-activated receptor-γ(PPAR-γ) signaling were also examined. The results showed that after treatment, the levels of fasting blood-glucose(FBG), triglyceride(TG) and low-density lipoprotein cholesterol(LDL-C) were significantly lower than those in the model group(P < 0.05), while the high-density lipoprotein cholesterol(HDL-C) level was significantly higher than those in the model group(P < 0.05). The levels of IL-8 and TNF-α in peripheral blood in the treatment group were significantly lower than those in the model group(P < 0.05). The macrophage infiltration and IL-6 levels in the adipose tissue of the treatment group were significantly lower than those in the model group(P < 0.05), but the IL-10 level was significantly higher than that in the model group(P < 0.05). The levels of PPAR-γ and adiponectin in the adipose tissue of the treatment group were significantly higher than those in the model group(P < 0.05). The findings suggest that Omentin-1 could improve the glycolipid metabolism and systemic inflammatory response which may be regulated through PPAR-γ signaling pathway.
In order to investigate the effect of Omentin-1 on mouse metabolic syndrom(MS) and its possible mechanism, we selected 6-8 weeks old SPF male BALB/c mice and established a MS model through high-fat and high-sugar diet. The mice were divided into the model group and the treatment group. The treatment group was given intraperitoneal injection of Omentin-1[8 μg/(kg·d)], and the model group was given an equal amount of normal saline. After 4 weeks of intervention, immunohistochemistry, ELISA and Western blotting were performed to evaluate the effects of Omentin-1 treatment on glucose and lipid metabolism, and systemic inflammation. In addition, the effect on inflammation in the visceral fat tissue and on peroxisome proliferators-activated receptor-γ(PPAR-γ) signaling were also examined. The results showed that after treatment, the levels of fasting blood-glucose(FBG), triglyceride(TG) and low-density lipoprotein cholesterol(LDL-C) were significantly lower than those in the model group(P < 0.05), while the high-density lipoprotein cholesterol(HDL-C) level was significantly higher than those in the model group(P < 0.05). The levels of IL-8 and TNF-α in peripheral blood in the treatment group were significantly lower than those in the model group(P < 0.05). The macrophage infiltration and IL-6 levels in the adipose tissue of the treatment group were significantly lower than those in the model group(P < 0.05), but the IL-10 level was significantly higher than that in the model group(P < 0.05). The levels of PPAR-γ and adiponectin in the adipose tissue of the treatment group were significantly higher than those in the model group(P < 0.05). The findings suggest that Omentin-1 could improve the glycolipid metabolism and systemic inflammatory response which may be regulated through PPAR-γ signaling pathway.
引文
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[14]Arman Y,Kirna K,Ugurlukisi B,et al.The effects of blood glucose regulation in omentin-1 levels among diabetic patients[J].Exp Clin Endocrinol Diabetes,2017,125(4):262-266.
[15]Marcelin G,Ferreira A,Liu Y,et al.A PDGFRα-mediated switch toward CD9highadipocyte progenitors controls obesityinduced adipose tissue fibrosis[J].Cell Metab,2017,25(3):673-685.
[16]Ishibashi K,Takeda Y,Nakatani E,et al.Activation of PPARγat an early stage of differentiation enhances adipocyte differentiation of MEFs derived from typeⅡdiabetic TSOD mice and alters lipid droplet morphology[J].Biol Pharm Bull,2017,40(6):852-859.
[17]Jeong W,Bae H,Lim W,et al.Adiponectin:A prosurvival and proproliferation signal that increases bovine mammary epithelial cell numbers and protects them from endoplasmic reticulum stress responses[J].J Anim Sci,2017,95(12):5278-5289.
[2]Saleem F,Rizvi SW.New therapeutic approaches in obesity and metabolic syndrome associated with polycystic ovary syndrome[J].Cureus,2017,9(11):e1844.
[3]Thomas D,Apovian C.Macrophage functions in lean and obese adipose tissue[J].Metabolism,2017,72:120-143.
[4]Huh JY,Jung I,Piao L,et al.8-Hydroxy-2-deoxyguanosine ameliorates high-fat diet-induced insulin resistance and adipocyte dysfunction in mice[J].Biochem Biophys Res Commun,2017,491(4):890-896.
[5]Bozkurt Doan S,ng9z Dede F,Balli U,et al.Levels of vaspin and omentin-1in gingival crevicular fluid as potential markers of inflammation in patients with chronic periodontitis and type 2diabetes mellitus[J].J Oral Sci,2016,58(3):379-389.
[6]Vu A,Sidhom MS,Bredbeck BC,et al.Evaluation of the relationship between circulating omentin-1concentrations and components of the metabolic syndrome in adults without type2diabetes or cardiovascular disease[J].Diabetol Metab Syndr,2014,6(1):4.
[7]Song J,Zhang H,Sun Y,et al.Omentin-1protects renal function of mice with type 2diabetic nephropathy via regulating miR-27a-Nrf2/Keap1axis[J].Biomed Pharmacother,2018,107:440-446.
[8]张琳,费雯婕,宋光耀.网膜素与代谢综合征[J].国际内分泌代谢杂志,2016,36(1):42-44.
[9]Prokudina ES,Maslov LN,Ivanov VV,et al.The role of reactive oxygen species in the pathogenesis of adipocyte dysfunction in metabolic syndrome.Prospects of pharmacological correction[J].Vestn Ross Akad Med Nauk,2017,72(1):11-16.
[10]Patel VS,Chan ME,Pagnotti GM,et al.Incorporating refractory period in mechanical stimulation mitigates obesityinduced adipose tissue dysfunction in adult mice[J].Obesity(Silver Spring),2017,25(10):1745-1753.
[11]Brunetti L,Di NC,Recinella L,et al.Effects of vaspin,chemerin and omentin-1on feeding behavior and hypothalamic peptide gene expression in the rat[J].Peptides,2011,32(9):1866-1871.
[12]Varlamov O,Bishop CV,Handu M,et al.Combined androgen excess and western-style diet accelerates adipose tissue dysfunction in young adult,female nonhuman primates[J].Hum Reprod,2017,32(9):1892-1902.
[13]Chen Q,Shang X,Yuan M,et al.Effect of atorvastatin on serum omentin-1in patients with coronary artery disease[J].Coron Artery Dis,2017,28(1):44-51.
[14]Arman Y,Kirna K,Ugurlukisi B,et al.The effects of blood glucose regulation in omentin-1 levels among diabetic patients[J].Exp Clin Endocrinol Diabetes,2017,125(4):262-266.
[15]Marcelin G,Ferreira A,Liu Y,et al.A PDGFRα-mediated switch toward CD9highadipocyte progenitors controls obesityinduced adipose tissue fibrosis[J].Cell Metab,2017,25(3):673-685.
[16]Ishibashi K,Takeda Y,Nakatani E,et al.Activation of PPARγat an early stage of differentiation enhances adipocyte differentiation of MEFs derived from typeⅡdiabetic TSOD mice and alters lipid droplet morphology[J].Biol Pharm Bull,2017,40(6):852-859.
[17]Jeong W,Bae H,Lim W,et al.Adiponectin:A prosurvival and proproliferation signal that increases bovine mammary epithelial cell numbers and protects them from endoplasmic reticulum stress responses[J].J Anim Sci,2017,95(12):5278-5289.
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