Resistance to visceral obesity is associated with increased locomotion in mice expressing an endothelial cell-specific fibroblast growth factor 1 transgene.
Center for Molecular Medicine, Maine Medical Center Research Institute
Mice, Animals, Obesity, Abdominal, Fibroblast Growth Factor 1, Transgenes, Fibroblasts, Locomotion, Endothelial Cells
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.
Keeley, Tyler; Kirov, Aleksandr; Koh, Woon Yuen; Demambro, Victoria; Bergquist, Ivy; Cotter, Jessica; Caradonna, Peter; Siviski, Matthew E; Best, Bradley; Henderson, Terry; Rosen, Clifford J; Liaw, Lucy; Prudovsky, Igor; and Small, Deena J, "Resistance to visceral obesity is associated with increased locomotion in mice expressing an endothelial cell-specific fibroblast growth factor 1 transgene." (2019). Maine Medical Center. 1686.