Abstract
Overdevelopment of visceral adipose is positively correlated with the etiology of obesity‐associated pathologies including cardiovascular disease and insulin resistance. However, identification of genetic, molecular, and physiological factors regulating adipose development and function in response to nutritional stress is incomplete. Fibroblast Growth Factor 1 (FGF1) is a cytokine expressed and released by both adipocytes and endothelial cells under hypoxia, thermal, and oxidative stress. Expression of Fibroblast Growth Factor 1 (FGF1) in adipose is required for normal depot development and remodeling. Loss of FGF1 leads to deleterious changes in adipose morphology, metabolism, and insulin resistance. Conversely, diabetic and obese mice injected with recombinant FGF1 display improvements in insulin sensitivity and a reduction in adiposity. We report in this novel, in vivo study that transgenic mice expressing an endothelial‐specific FGF1 transgene (FGF1‐Tek) are resistant to high‐fat diet‐induced abdominal adipose accretion and are more glucose‐tolerant than wild‐type control animals. Metabolic chamber analyses indicate that suppression of the development of visceral adiposity and insulin resistance was not associated with alterations in appetite or resting metabolic rate in the FGF1‐Tek strain. Instead, FGF1‐Tek mice display increased locomotor activity that likely promotes the utilization of dietary fatty acids before they can accumulate in adipose and liver. This study provides insight into the impact that genetic differences dictating the production of FGF1 has on the risk for developing obesity‐related metabolic disease in response to nutritional stress.
Highlights
Diets high in carbohydrates and/or saturated fat often result in the development of obesity and obesity-related pathologies, patterns of adipose accretion, and incidence of metabolic disease differ among individuals with similar dietary and exercise regimens (Bouret et al 2015)
Fibroblast Growth Factor 1 (FGF1)-Tek mice express an endothelial-cell specific, doxycycline-inducible FGF1 transgene that results in the secretion of FGF1 into all vascularized tissues including adipose (Kirov et al 2012)
Since the FGF1-Tek strain was backcrossed to the FVB/N strain, these animals were used as wild-type controls (FVB Control) (Kirov et al 2012)
Summary
Diets high in carbohydrates and/or saturated fat often result in the development of obesity and obesity-related pathologies, patterns of adipose accretion, and incidence of metabolic disease differ among individuals with similar dietary and exercise regimens (Bouret et al 2015). Transcriptome analyses have identified a variety of genes encoding metabolic hormones as well as proteins associated with adipogenesis, angiogenesis and inflammation that are differentially regulated by diet, and by sex and disease (Urs et al 2004; Koza et al 2006; Hagobian et al 2009; Viguerie et al 2012). Mice lacking a functional fgf gene(fgf1À/À) display defects in adipose remodeling and vascularization, insulin resistance, and steatosis in response to diets high in saturated fats (Jonker et al 2012). Both parenteral and intracerebroventricular administration of recombinant FGF1 improves insulin sensitivity and lipid metabolism in diabetic mice, further supporting a role for FGF1 as a regulator of metabolic homeostasis (Suh et al 2014; Scarlett et al 2016). The ability of transgenically expressed FGF1 to prevent the deleterious effects of excess intake of saturated fats on adipose development, glucose homeostasis, and lipid metabolism in vivo has yet to be reported
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