Browsing by Subject "Adiposity"
Now showing 1 - 4 of 4
- Results Per Page
- Sort Options
Item Loss of Ventromedial Hypothalamic Leptin Receptors Results in Increased Adiposity and a Metabolic Syndrome(2008-05-12) Bingham, Nathan Christian; Parker, Keith L.Obesity is a leading health problem here in the United States and in other developing countries. Obesity is a risk factor for several life-threatening conditions including Type II diabetes, hypertension, and cardiovascular disease. Given the growing obesity epidemic, understanding the mechanisms whereby the central nervous system monitors and regulates energy homeostasis has become a major focus of scientific research in the last several decades. The discovery that mice fed a low fat diet exhibit significantly increased adipose mass with no difference in weight compared to wild-type littermates. Further, these mice exhibit a metabolic syndrome including mild steatosis, dyslipidemia, and hyperleptinemia. From a young age, Lepr KOleptin, an adipocyte-derived hormone, acts on the brain to suppress appetite and stimulate energy expenditure greatly extended our understanding of such mechanisms. The leptin receptor is expressed in a number of hypothalamic nuclei known to play a role in energy homeostasis. While much work has focused on leptin's actions in the arcuate nucleus, other sites have received substantially less attention. Here, I report that mice lacking leptin receptors within the ventromedial hypothalamic nucleus (Lepr KOVMH) develop increased adiposity and a metabolic syndrome. Lepr KOVMH mice fed high fat rodent chow show an increased sensitivity to diet-induced obesity, while Lepr KOVMH mice are hyperinsulinemic and eventually become glucose intolerant. These data demonstrate that Lepr KOVMH mice are a novel genetic model of obesity and may be used for the study of energy partitioning, lipogenesis, and central leptin signaling.Item Metabolic Outcomes of Aging and Obesity: A Longitudinal Study of the Dallas Heart Study Cohort(2023-01-31) Davis, Parker; Yokoo, TakeshiSequestration of body fat into subcutaneous and intra- abdominal (visceral) compartments influences metabolic outcomes. Visceral fat contains more proinflammatory cytokines, and is more metabolically active, with a greater propensity for lipolysis. It is associated with hypertriglyceridemia, increased VLDL synthesis, liver insulin resistance, and reduced HDL cholesterol, and more strongly predicts mortality (Tchernof et al., 2013; Browning et al., 2004; Chalasani et al., 2018; Ibrahim, 2009). The purpose of this study is to examine adiposity in subjects of the Dallas Heart Study (DHS1 ran 1999-2000, DHS2 began shortly after) and extend the findings in the prospective, longitudinal Dallas Heart and Minds Study (2020- ), allowing the effects of changes in adiposity to be tracked over a nearly 20-year period. We hypothesize that visceral adiposity increases with age and predicts the development of cardiovascular disease and the metabolic syndrome. Adiposity analysis was undertaken on DHS subjects who completed an abdominal MRI in DHS1 and unique subjects who had completed a whole-body MRI in DHS2. DHMS subjects were former DHS subjects who had an abdominal MRI in DHS and whole-body MRI in DHMS. DHS subjects were scanned using a 1.5T MRI from diaphragm to pelvis with contiguous 10mm slices. Fat contouring was performed on a single slice at L2-L3 using Medis Mass software; DHMS subjects were scanned similarly. Adiposity segmentations in DHMS were performed on the slice corresponding with each subject's DHS segmentation. A prospective method of fat mass prediction from a single MRI slice was used to convert fat volumes to mass (Abate et al., 1997; Neeland et al., 2016). Changes in subcutaneous and visceral fat between DHS and DHMS were calculated to determine the effects on metabolic health. 135 of 254 contoured DHMS subjects had contours in DHS1/2. DHMS subjects had an average weight gain of 1.245kg, BMI increase of 0.792kg/m2, increase in subcutaneous adipose cross-sectional area of 67cm2, and increase in visceral adipose cross-sectional area of 31.102cm2. The change in weight was significantly correlated with changes in subcutaneous (r=0.74, p=0) and visceral adiposity (r=0.59, p=0). Changes in subcutaneous and visceral adiposity were significantly correlated (r=0.23, p=0.006). Finally, DHMS subjects with HOMA IR >2.73 during DHS1/2 had significant percent decreases in weight (p=0.003), subcutaneous adiposity (p<0.001), and visceral adiposity (p<0.001), in contrast to the trends described above.Item [News](1988-06-23) Harrell, AnnItem Sexually Dimorphic Role of G Protein-Coupled Estrogen Receptor (GPER) in Modulating Energy Homeostasis(2014-02-04) Carstens, Elizabeth J.; Davis, Kathryn E.; Irani, Boman G.; Gent, Lana M.; Hahner, Lisa M.; Clegg, Deborah J.The classical estrogen receptors, estrogen receptor -α- and estrogen receptor β, are well established in the regulation of body weight and energy homeostasis in both male and female mice, whereas, the role for a G protein-coupled estrogen receptor 1 (GPER) as a modulator of energy homeostasis remains controversial. This study sought to determine whether gene deletion of GPER (GPER KO) alters body weight, body adiposity, food intake, and energy homeostasis in both males and females. Male mice lacking GPER developed moderate obesity and larger adipocyte size beginning at 8 weeks of age, with significant reductions in energy expenditure, but not food intake or adipocyte number. Female GPER KO mice developed increased body weight relative to WT females a full 6 weeks later than the male GPER KO mice. Female GPER KO mice also had reductions in energy expenditure, but not significant increases in body fat content. Consistent with their decrease in energy expenditure, GPER KO males and females showed significant reductions in two brown fat thermogenic proteins. GPER KO females, prior to their divergence in body weight, were less sensitive than WT females to the feeding-inhibitory effects of leptin and CCK. Additionally, body weight was not modulated fully by ovariectomy or estradiol replacement in GPER KO mice. Estradiol treatment activated phosphorylated extracellular signal-regulated kinase (pERK) in WT but not GPER KO females. For the first time, GPER expression was found in the adipocyte but not the stromal fraction of adipose tissue. Together, these results provide new information elucidating a sexual dimorphism in GPER function in the development of postpubertal energy balance.