Abstract
Postnatal overconsumption of fat is believed to increase the susceptibility to metabolic disease in the later life. Here we examined whether prior exposure to high fat (HF) in the adulthood may also accelerate the development of metabolic disorders in mice. Adult mice (12 weeks) were pre-exposed to two episodes of an HF diet each for 2 weeks followed by 2 weeks of washout with a low-fat diet. The mice were then fed the same HF diet for 6 weeks. Unexpectedly, prior exposures to HF diet significantly alleviated body weight gain, visceral adiposity and glucose/insulin intolerance during the period of last HF feeding. These protective effects were evident without changing calorie intake and were specific for HF, but not high fructose (HFru) diet. Following the HF prior exposures was increases in plasma fibroblast growth factor 21 (FGF21), the expressions of phospho-AMP-activated protein kinase (pAMPK), mitochondrial complex II and the expression of uncoupling protein (UCP) 3 in muscle and UCP1 and Sirtuin 1 (SIRT1) in adipose tissue. However, in the liver there was no significant change in pAMPK, SIRT1 expression or the capacity of glucose production. These findings indicated that, instead of exacerbating metabolic conditions, prior exposures to HF diet lead to the preconditioning against subsequent overload of HF, possibly involving FGF21-associated enhancement of markers for metabolic capacity in muscle and adipose tissue. This paradoxical phenomenon may offer a unique paradigm to identify factors and explore dietary ingredients with beneficial effects for the control of the metabolic syndrome in humans.
Highlights
Central obesity and insulin resistance are fundamental to the pathogenesis of the metabolic syndrome [1,2]
The present study investigated whether prior exposures to high fat (HF) diet in the adulthood may induce long-lasting risk to the development of the metabolic syndrome
Based on the reported risk of the early life experience like this [10,11,12,13], we had hypothesised that prior feeding with an HF diet would exacerbate the metabolic syndrome in the subsequent response to the HF diet
Summary
Central obesity and insulin resistance are fundamental to the pathogenesis of the metabolic syndrome [1,2]. Increased consumption of high-calorie diets and decreased energy expenditure (such as in a sedentary lifestyle) are major risk factors of obesity [1,2]. One of the most important dietary compositions leading to obesity and insulin resistance is the high fat (HF) content in diet, the lard-based HF diet [3,4]. It remains unclear that whether prior exposure to HF diets in adulthood has long-term metabolic effects after the cessation of the HF feeding. There is emerging evidence to suggest that various environmental factors may have long-term impacts on the metabolic syndrome. It has been reported that calorie restriction can induce long-term weight loss [9]
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