Abstract
Obesity causes white adipose tissue (WAT) inflammation and insulin resistance in some, but not all individuals. Here, we used a mouse model of early postnatal overfeeding to determine the role of neonatal nutrition in lifelong WAT inflammation and metabolic dysfunction. C57BL/6J mice were reared in small litters of 3 (SL) or normal litters of 7 pups (NL) and fed either regular chow or a 60% high fat diet (HFD) from 5 to 17 weeks. At weaning, SL mice did not develop WAT inflammation despite increased fat mass, although there was an up-regulation of WAT Arg1 and Tlr4 expression. On HFD, adult SL mice had greater inguinal fat mass compared to NL mice, however both groups showed similar increases in visceral fat depots and adipocyte hypertrophy. Despite the similar levels of visceral adiposity, SL-HFD mice displayed greater impairments in glucose homeostasis and more pronounced hepatic steatosis compared to NL-HFD mice. In addition, WAT from SL mice fed a HFD displayed greater crown-like structure formation, increased M1 macrophages, and higher cytokine gene expression. Together, these data suggest that early postnatal overnutrition may be a critical determinant of fatty liver and insulin resistance in obese adults by programming the inflammatory capacity of adipose tissue.
Highlights
The prevalence of overweight and obesity has increased at an alarming rate in countries that have adopted a Western lifestyle, which includes overconsumption of energy-rich and nutrient-poor food [1,2]
We investigated adipose tissue macrophage infiltration using immunostaining for the macrophage marker F4/80
Because obesity induces a phenotypic switch in adipose tissue macrophage polarization from an M2-polarized state to an M1 pro-inflammatory state [23], we assessed M1- and M2-related gene expression in sWAT of small litters (SL) and normal litters (NL) at P21. mRNA expression of the anti-inflammatory gene Arg1 was 5.4-fold increased (Fig 1G; P
Summary
The prevalence of overweight and obesity has increased at an alarming rate in countries that have adopted a Western lifestyle, which includes overconsumption of energy-rich and nutrient-poor food [1,2]. Such lifestyle changes affect children, which raises major health concerns because obese children and adolescents are more likely to become obese adults [3]. Obesity is the primary risk factor for the development of type 2 diabetes by causing inulin resistance, which results in a greater demand of the pancreas to secrete insulin and eventually β-cell failure in susceptible individuals [4]. Obesity is not always sufficient to cause insulin.
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