Ramdhave Anup S, Ojha Shreesh, Nandave Mukesh
SPP School of Pharmacy & Technology Management, SVKM's NMIMS Mumbai, India.
Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University Al Ain, UAE.
Am J Transl Res. 2017 Mar 15;9(3):830-844. eCollection 2017.
Emerging evidence suggests that, dysregulation of fatty acid synthase (FASN) and insulin-like growth factor-1 (IGF-1) could play a vital role in pathology of various diseases. Our aim was to determine the changes in FASN and IGF-1 levels concomitant to long term feeding of HFD in either sex. Male and female mice were fed either HFD or LFD for a period of 16 weeks. During this period, physiological, biochemical, and histological parameters were evaluated. Mice fed with HFD showed a significant gain in body weight, body mass index, energy intake, and abdominal circumference. These changes were accompanied by compromised glucose and insulin tolerance, hyperinsulinemia, dyslipidemia, elevated plasma IL-6, and TNF-α concentration. Histologically, hepatocytes showed an elevated fat accumulation, appended by an increase in plasma activities of liver enzymes. Pancreas showed upsurge in number of β-cells with subsequent increase in size of islet implying its compromised state. While the kidney showed mild tubulointerstitial fibrosis indicating initiation of kidney impairment. These metabolic perturbations were related to the energy intake which was higher in males as compared to females. This led to a proportional rise in plasma as well as liver FASN and IGF-1 in HFD fed mice. Within both sexes, mice fed with HFD developed features of non-alcoholic steatohepatitis (NASH), hyperinsulinemia, dyslipidemia, impaired glucose and insulin tolerance but the magnitude of these abnormalities was found to be less in female mice. This variation in magnitude could be attributed to the difference in energy intake and ultimately its effect on FASN and IGF-1 levels.
新出现的证据表明，脂肪酸合酶（FASN）和胰岛素样生长因子-1（IGF-1）的失调可能在各种疾病的病理过程中起关键作用。我们的目的是确定长期喂食高脂饮食（HFD）对雌雄小鼠FASN和IGF-1水平的影响。将雄性和雌性小鼠分别喂食HFD或低脂饮食（LFD）16周。在此期间，评估生理、生化和组织学参数。喂食HFD的小鼠体重、体重指数、能量摄入和腹围显著增加。这些变化伴随着葡萄糖和胰岛素耐受性受损、高胰岛素血症、血脂异常、血浆白细胞介素-6和肿瘤坏死因子-α浓度升高。组织学上，肝细胞脂肪堆积增加，同时肝酶血浆活性升高。胰腺β细胞数量增加，随后胰岛大小增加，表明其功能受损。而肾脏显示轻度肾小管间质纤维化，提示肾脏损害开始。这些代谢紊乱与能量摄入有关，雄性小鼠的能量摄入高于雌性小鼠。这导致喂食HFD的小鼠血浆和肝脏中FASN和IGF-1成比例上升。在两性中，喂食HFD的小鼠出现了非酒精性脂肪性肝炎（NASH）、高胰岛素血症、血脂异常、葡萄糖和胰岛素耐受性受损等特征，但发现雌性小鼠这些异常的程度较轻。这种程度的差异可能归因于能量摄入的差异以及最终对FASN和IGF-1水平的影响。
