We present a 50-year-old female who was evaluated for the symptoms of thyrotoxicosis. She had low thyroid stimulating hormone (TSH) 0.02 with normal free thyroxine (FT4) 1.
View Article and Find Full Text PDFObjective: The aim of this study was to determine whether downstream [peroxisome proliferator-activated-receptor alpha (PPARα) and the G-protein coupled receptor, GPR119] and upstream (a fatty acid translocase, CD36) signaling targets of N-oleoylethanolamide (OEA) were necessary for weight loss, metabolic improvements, and diet preference following vertical sleeve gastrectomy (VSG).
Summary Background Data: OEA is an anorectic N-acylethanolamine produced from dietary fats within the intestinal lumen that can modulate lipid metabolism, insulin secretion, and energy expenditure by activating targets such as PPARα and GPR119.
Methods: Diet-induced obese mice, including wild-type or whole body knockout (KO) of PPARα, GPR119, and CD36, were stratified to either VSG or sham surgery before body weight, body composition, diet preference, and glucose and lipid metabolic endpoints were assessed.
Exercise is an effective therapy against the metabolic syndrome. However, the molecular pathways underlying the advantageous effects of exercise are elusive. Glucagon receptor signaling is essential for exercise benefits, and recent evidence indicates that a downstream effector of glucagon, fibroblast growth factor 21 (FGF21), is implicated in this response.
View Article and Find Full Text PDFObjective: Melanocortin-4 receptors (MC4Rs) are highly expressed by dopamine-secreting neurons of the mesolimbic tract, but their functional role has not been fully resolved. Voluntary wheel running (VWR) induces adaptations in the mesolimbic dopamine system and has a myriad of long-term beneficial effects on health. In the present experiments we asked whether MC4R function regulates the effects of VWR, and whether VWR ameliorates MC4R-associated symptoms of the metabolic syndrome.
View Article and Find Full Text PDFAlthough ginseng has been reported to ameliorate hyperglycemia in animal models and clinical studies, the molecular mechanisms are largely unknown. We previously reported that chronic treatment with ginsenoside Rb1 (Rb1), a major component of ginseng, significantly reduced fasting glucose and improved glucose tolerance in high-fat diet (HFD)-induced obese rats. These effects were greater than those observed in pair-fed rats, suggesting a direct effect of Rb1 on glucose homeostasis, and this possibility was confirmed in the present study.
View Article and Find Full Text PDFPurpose Of Review: New evidence has recently supported the notion that brown adipose tissue (BAT) is present in adult humans and can play a prominent role in the regulation of body weight and metabolism. This has renewed the efforts to understand the physiologic mechanisms by which BAT is activated, which in turn could provide new therapeutic strategies for obesity and diabetes.
Recent Findings: BAT mass and activity are positively correlated with measures of metabolic health in rodents and humans; however, the amount of functional BAT in adult humans is highly variable with less found in overweight and obese individuals.
We showed recently that apoA-IV improves glucose homeostasis by enhancing pancreatic insulin secretion in the presence of elevated levels of glucose. Therefore, examined whether apolipoprotein A-IV (apoA-IV) also regulates glucose metabolism through the suppression of hepatic gluconeogenesis. The ability of apoA-IV to lower gluconeogenic gene expression and glucose production was measured in apoA-IV(-/-) and wild-type mice and primary mouse hepatocytes.
View Article and Find Full Text PDFBariatric procedures vary in efficacy, but overall are more effective than behavioral and pharmaceutical treatment. Roux-en-Y gastric bypass causes increased secretion of glucagon-like peptide 1 (GLP-1) and reduces body weight (BW) more than adjustable gastric banding (AGB), which does not trigger increased GLP-1 secretion. Since GLP-1-based drugs consistently reduce BW, we hypothesized that GLP-1 receptor (GLP-1R) agonists would augment the effects of AGB.
View Article and Find Full Text PDFBackground: The contribution of liver glycogen catabolism to hyperglycemia and glucose intolerance induced by pharmacological hypercortisolism were investigated.
Methods: For this purpose, adult male Wistar rats that received 1.0 mg/kg dexamethasone (DEX) ip at 8:00 a.
Helper-dependent adenoviral vectors (HD Ad) hold extreme promise for gene therapy of human diseases. All viral genes are deleted in HD Ad vectors, and therefore, the presence of a helper virus is required for their production. Current methods to minimize helper contamination in large-scale preparations rely on the use of the Cre/loxP system.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
June 2012
Apolipoprotein A-IV (apoA-IV) is secreted by the small intestine in response to fat absorption. Here we demonstrate a potential role for apoA-IV in regulating glucose homeostasis. ApoA-IV-treated isolated pancreatic islets had enhanced insulin secretion under conditions of high glucose but not of low glucose, suggesting a direct effect of apoA-IV to enhance glucose-stimulated insulin release.
View Article and Find Full Text PDFBackground: The aim of the current investigation was to examine the effects of consuming a low-carbohydrate high-fat diet (LC-HFD) in combination with daily exercise on body weight, body composition, endocrine control of the energy balance system and exercise capacity in adolescent and mature rats.
Method: Adolescent (n=23) and mature rats (n=16) were maintained on either a standard chow diet (CH) or a LC-HFD for a period of ten days prior to daily exercise training for 21 days in forced running wheel system. At the end of the 21 day training sessions all rats took part in an exercise performance test where time to exhaustion was measured.
It is well established that the development of insulin resistance shows a temporal sequence in different organs and tissues. Moreover, considering that the main aspect of insulin resistance in liver is a process of glucose overproduction from gluconeogenesis, we investigated if this metabolic change also shows temporal sequence. For this purpose, a well-established experimental model of insulin resistance induced by high-fat diet (HFD) was used.
View Article and Find Full Text PDFAims/hypothesis: We examined the physiological mechanisms by which cannabinoid receptor 1 (CB1) antagonism improves glucose metabolism and insulin sensitivity independent of its anorectic and weight-reducing effects, as well as the effects of CB1 antagonism on brown adipose tissue (BAT) function.
Methods: Three groups of diet-induced obese mice received for 1 month: vehicle; the selective CB1 antagonist SR141716; or vehicle/pair-feeding. After measurements of body composition and energy expenditure, mice underwent euglycaemic-hyperinsulinaemic clamp studies to assess in vivo insulin action.
Dysregulation of the endocannabinoid system (ECS) is a universal and, perhaps, causative feature of obesity. Central nervous system (CNS) circuits that regulate food intake were initially believed to be the targets for dysregulation. However, it is increasingly evident that endocannabinoids affect food intake, energy expenditure and substrate metabolism by acting on peripheral sites.
View Article and Find Full Text PDFThe functions of leptin receptors (LRs) are cell-type specific. At the blood-brain barrier, LRs mediate leptin transport that is essential for its CNS actions, and both endothelial and astrocytic LRs may be involved. To test this, we generated endothelia specific LR knockout (ELKO) and astrocyte specific LR knockout (ALKO) mice.
View Article and Find Full Text PDFObjective: Cholecystokinin (CCK) is released in response to lipid intake and stimulates insulin secretion. We hypothesized that CCK deficiency would alter the regulation of insulin secretion and glucose homeostasis.
Research Design And Methods: We used quantitative magnetic resonance imaging to determine body composition and studied plasma glucose and insulin secretion of CCK gene knockout (CCK-KO) mice and their wild-type controls using intraperitoneal glucose and arginine infusions.
The efficacy of exercise as primary prevention of obesity is the subject of intense investigation. Here, we show that voluntary exercise in a mouse strain susceptible to diet-induced obesity (C57B6J) decreases fat mass and increases energy expenditure. In addition, exercise attenuates obesity in mice fed a high-fat diet (HFD).
View Article and Find Full Text PDFOlfaction is an integral part of feeding providing predictive cues that anticipate ingestion. Although olfactory function is modulated by factors such as prolonged fasting, the underlying neural mechanisms remain poorly understood. We recently identified ghrelin receptors in olfactory circuits in the brain.
View Article and Find Full Text PDFRoux-en-y gastric bypass (RYGB) surgery rapidly improves glucose tolerance and reverses insulin resistance in obese patients. It has been hypothesized that this effect is mediated by the diversion of nutrients from the proximal small intestine. We utilized duodenal-jejunal bypass (DJB) as a modification of gastric bypass to determine the effect of nutrient diversion from the foregut without gastric restriction on insulin resistance in obese rats.
View Article and Find Full Text PDFThe Mouse Metabolic Phenotyping Center (MMPC) Consortium was established to address the need to characterize the growing number of mouse models of metabolic diseases, particularly diabetes and obesity. A goal of the MMPC Consortium is to propose standard methods for assessing metabolic phenotypes in mice. In this article, we discuss issues pertaining to the design and performance of various tests of glucose metabolism.
View Article and Find Full Text PDFObjective: Olanzapine (OLZ) is an atypical antipsychotic whose clinical efficacy is hampered by side effects including weight gain and diabetes. Recent evidence shows that OLZ alters insulin sensitivity independent of changes in body weight and composition. The present study addresses whether OLZ-induced insulin resistance is driven by its central actions.
View Article and Find Full Text PDFKielmeyera coriacea Mart. (Clusiaceae), known as "Pau Santo", is used to treat several tropical diseases. The hydroethanolic extract (HE) of Kielmeyera coriacea stems and its semi-pure dichloromethane constituent (DCM) produced an anti-immobility effect in rats submitted to the forced swimming test (FST), suggesting a antidepressant-like profile.
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