Abstract
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.