scholarly journals Intracerebroventricular injection of citrate inhibits hypothalamic AMPK and modulates feeding behavior and peripheral insulin signaling

2008 ◽  
Vol 198 (1) ◽  
pp. 157-168 ◽  
Author(s):  
Graziela R Stoppa ◽  
Maristela Cesquini ◽  
Erika A Roman ◽  
Patrícia O Prada ◽  
Adriana S Torsoni ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Adipose Tissue ◽  
Protein Kinase ◽  
Body Weight Loss ◽  
Control Group ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Akt Phosphorylation ◽  
Hypothalamic Cells ◽  
Feeding Control

We hypothesized that citrate might modulate the AMP-activated protein kinase/acetyl-CoA carboxylase (AMPK)/(ACC) pathway and participate in neuronal feeding control and glucose homeostasis. To address this issue, we injected citrate into the lateral ventricle of rats. Intracerebroventricular (ICV) injection of citrate diminished the phosphorylation of hypothalamic AMPK/ACC, increased the expression of anorexigenic neuropeptide (pro-opiomelanocortin and corticotropin-releasing hormone), elevated the level of malonyl-CoA in the hypothalamus, and reduced food intake. No change was observed in the concentration of blood insulin after the injection of citrate. With a euglycemic–hyperinsulinemic clamp, the glucose infusion rate was higher in the citrate group than in the control group (28.6±0.8 vs 19.3±0.2 mU/kg body weight/min respectively), and so was glucose uptake in skeletal muscle and the epididymal fat pad. Concordantly, insulin receptor (IR), IR substrate type 1 (IRS1), IRS2, and protein kinase B (AKT) phosphorylation in adipose tissue and skeletal muscle was improved by citrate ICV treatment. Moreover, the treatment with citrate for 7 days promoted body weight loss and decreased the adipose tissue. Our results suggest that citrate and glucose may serve as signals of energy and nutrient availability to hypothalamic cells.

scholarly journals Metabolic Consequences of Neuronal HIF1α-Deficiency in Mediobasal Hypothalamus in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Azmat Rozjan ◽  
Weibi Shan ◽  
Qiaoling Yao
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Mrna Expression ◽  
Density Lipoprotein ◽  
The Body ◽  
Control Group ◽  
Mediobasal Hypothalamus ◽  
Akt Phosphorylation ◽  
Glucose And Lipid Metabolism ◽  
Mrna Expression Levels

ObjectiveThis study aims to investigate whether hypoxia-inducible factor 1α (HIF1α) in the neurons of the mediobasal hypothalamus is involved in the regulation of body weight, glucose, and lipid metabolism in mice and to explore the underlying molecular mechanisms.MethodsHIF1αflox/flox mice were used. The adeno-associated virus that contained either cre, GFP and syn, or GFP and syn (controls) was injected into the mediobasal hypothalamus to selectively knock out HIF1α in the neurons of the mediobasal hypothalamus. The body weight and food intake were weighed daily. The levels of blood glucose, insulin, total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein (HDL), and low-density lipoprotein (LDL)were tested. Intraperitoneal glucose tolerance test (IPGTT) was performed. The insulin-stimulated Akt phosphorylation in the liver, epididymal fat, and skeletal muscle were examined. Also, the mRNA expression levels of HIF1α, proopiomelanocortin (POMC), neuropeptide Y (NPY), and glucose transporter protein 4 (Glut4) in the hypothalamus were checked.ResultsAfter selectively knocking out HIF1α in the neurons of the mediobasal hypothalamus (HIF1αKOMBH), the body weights and food intake of mice increased significantly compared with the control mice (p < 0.001 at 4 weeks). Compared with that of the control group, the insulin level of HIF1αKOMBH mice was 3.5 times higher (p < 0.01). The results of the IPGTT showed that the blood glucose level of the HIF1αKOMBH group at 20–120 min was significantly higher than that of the control group (p < 0.05). The serum TC, FFA, HDL, and LDL content of the HIF1αKOMBH group was significantly higher than those of the control group (p < 0.05). Western blot results showed that compared with those in the control group, insulin-induced AKT phosphorylation levels in liver, epididymal fat, and skeletal muscle in the HIF1αKOMBH group were not as significantly elevated as in the control group. Reverse transcription-polymerase chain reaction (RT-PCR) results in the whole hypothalamus showed a significant decrease in Glut4 mRNA expression. And the mRNA expression levels of HIF1α, POMC, and NPY of the HIF1αKOMBH group decreased significantly in ventral hypothalamus.ConclusionsThe hypothalamic neuronal HIF1α plays an important role in the regulation of body weight balance in mice under normoxic condition. In the absence of hypothalamic neuronal HIF1α, the mice gained weight with increased appetite, accompanied with abnormal glucose and lipid metabolism. POMC and Glut4 may be responsible for this effect of HIF1α.

scholarly journals Novel α-MSH analog causes weight loss in obese rats and minipigs and improves insulin sensitivity

2013 ◽  
Vol 220 (2) ◽  
pp. 97-107 ◽  
Author(s):  
Keld Fosgerau ◽  
Kirsten Raun ◽  
Cecilia Nilsson ◽  
Kirsten Dahl ◽  
Birgitte S Wulff
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Food Intake ◽  
Body Weight Loss ◽  
Vehicle Control ◽  
Glucose Disposal ◽  
Control Group ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Peptide Agonist

Obesity is a major burden to people and to health care systems around the world. The aim of the study was to characterize the effect of a novel selective α-MSH analog on obesity and insulin sensitivity. The subchronic effects of the selective MC4-R peptide agonist MC4-NN1-0182 were investigated in diet-induced obese (DIO) rats and DIO minipigs by assessing the effects on food intake, energy consumption, and body weight. The acute effect of MC4-NN1-0182 on insulin sensitivity was assessed by a euglycemic–hyperinsulinemic clamp study in normal rats. Three weeks of treatment of DIO rats with MC4-NN1-0182 caused a decrease in food intake and a significant decrease in body weight 7±1%,P<0.05 compared with 3±1% increase with the vehicle control. In DIO minipigs, 8 weeks of treatment with MC4-NN1-0182 resulted in a body weight loss of 13.3±2.5 kg (13±3%), whereas the vehicle control group had gained 3.7±1.4 kg (4±1%). Finally, clamp studies in normal rats showed that acute treatment with MC4-NN1-0182 caused a significant increase in glucose disposal (Rd) compared with vehicle control (Rd, mg/kg per min, 17.0±0.7 vs 13.9±0.6,P<0.01). We demonstrate that treatment of DIO rats or minipigs with a selective MC4-R peptide agonist causes weight loss. Moreover, we have demonstrated weight-independent effects on insulin sensitivity. Our observations identify MC4 agonism as a viable target for the treatment of obesity and insulin resistance.

scholarly journals Mechanism of Body Weight Reducing Effect of Oral Boric Acid Intake

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Erhan Aysan ◽  
Fikrettin Sahin ◽  
Dilek Telci ◽  
Merve Erdem ◽  
Mahmut Muslumanoglu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Body Weight ◽  
Adipose Tissue ◽  
Boric Acid ◽  
Tap Water ◽  
Acid Group ◽  
Control Group ◽  
Acid Intake ◽  
Brown Adipose

Objective. The effect of oral boric acid intake on reducing body weight has been previously demonstrated although the mechanism has been unclear. This research study reveals the mechanism.Subjects. Twelve mice were used, in groups of six each in the control and study groups. For five days, control group mice drank standard tap water while during the same time period the study group mice drank tap water which contains 0.28 mg/250 mL boric acid. After a 5-day period, gene expression levels for uncoupling proteins (UCPs) in the white adipose tissue (WAT), brown adipose tissue (BAT), and skeletal muscle tissue (SMT) and total body weight changes were analyzed.Results. Real time PCR analysis revealed no significant change in UCP3 expressions, but UCP2 in WAT (: 0.0317), BAT (: 0.014), and SMT (: 0.0159) and UCP1 in BAT (: 0.026) were overexpressed in the boric acid group. In addition, mice in the boric acid group lost body weight (mean 28.1%) while mice in the control group experienced no weight loss but a slight weight gain (mean 0.09%, ).Conclusion. Oral boric acid intake causes overexpression of thermogenic proteins in the adipose and skeletal muscle tissues. Increasing thermogenesis through UCP protein pathway results in the accelerated lipolysis and body weight loss.

Role of the AMP-activated protein kinase in regulating fatty acid metabolism during exerciseThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 34 (3) ◽  
pp. 315-322 ◽  
Author(s):  
Gregory R. Steinberg
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Moderate Intensity ◽  
Amp Activated Protein Kinase

During moderate-intensity exercise, fatty acids are the predominant substrate for working skeletal muscle. The release of fatty acids from adipose tissue stores, combined with the ability of skeletal muscle to actively fine tune the gradient between fatty acid and carbohydrate metabolism, depending on substrate availability and energetic demands, requires a coordinated system of metabolic control. Over the past decade, since the discovery that AMP-activated protein kinase (AMPK) was increased in accordance with exercise intensity, there has been significant interest in the proposed role of this ancient stress-sensing kinase as a critical integrative switch controlling metabolic responses during exercise. In this review, studies examining the role of AMPK as a regulator of fatty acid metabolism in both adipose tissue and skeletal muscle during exercise will be discussed. Exercise induces activation of AMPK in adipocytes and regulates triglyceride hydrolysis and esterfication through phosphorylation of hormone sensitive lipase (HSL) and glycerol-3-phosphate acyl-transferase, respectively. In skeletal muscle, exercise-induced activation of AMPK is associated with increases in fatty acid uptake, phosphorylation of HSL, and increased fatty acid oxidation, which is thought to occur via the acetyl-CoA carboxylase-malony-CoA-CPT-1 signalling axis. Despite the importance of AMPK in regulating fatty acid metabolism under resting conditions, recent evidence from transgenic models of AMPK deficiency suggest that alternative signalling pathways may also be important for the control of fatty acid metabolism during exercise.

Influence of diet and exercise on skeletal muscle and visceral adipose tissue in men

1996 ◽  
Vol 81 (6) ◽  
pp. 2445-2455 ◽  
Author(s):  
Robert Ross ◽  
John Rissanen ◽  
Heather Pedwell ◽  
Jennifer Clifford ◽  
Peter Shragge
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Whole Body ◽  
Relative Reduction ◽  
Body Regions ◽  
Diet And Exercise ◽  
Magnetic Resonance Imaging Mri ◽  
Visceral Adipose

Ross, Robert, John Rissanen, Heather Pedwell, Jennifer Clifford, and Peter Shragge. Influence of diet and exercise on skeletal muscle and visceral adipose tissue in men. J. Appl. Physiol. 81(6): 2445–2455, 1996.—The effects of diet only (DO) and diet combined with either aerobic (DA) or resistance (DR) exercise on subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), lean tissue (LT), and skeletal muscle (SM) tissue were evaluated in 33 obese men (DO, n= 11; DA, n = 11; DR, n = 11). All tissues were measured by using a whole body multislice magnetic resonance imaging (MRI) model. Within each group, significant reductions were observed for body weight, SAT, and VAT ( P < 0.05). The reductions in body weight (∼10%) and SAT (∼25%) and VAT volume (∼35%) were not different between groups ( P > 0.05). For all treatments, the relative reduction in VAT was greater than in SAT ( P < 0.05). For the DA and DR groups only, the reduction in abdominal SAT (∼27%) was greater ( P < 0.05) than that observed for the gluteal-femoral region (∼20%). Conversely, the reduction in VAT was uniform throughout the abdomen regardless of treatment ( P > 0.05). MRI-LT and MRI-SM decreased both in the upper and lower body regions for the DO group alone ( P < 0.05). Peak O2 uptake (liters) was significantly improved (∼14%) in the DA group as was muscular strength (∼20%) in the DR group ( P< 0.01). These findings indicate that DA and DR result in a greater preservation of MRI-SM, mobilization of SAT from the abdominal region, by comparison with the gluteal-femoral region, and improved functional capacity when compared with DO in obese men.

scholarly journals Amyotrophy Induced by a High-Fat Diet Is Closely Related to Inflammation and Protein Degradation Determined by Quantitative Phosphoproteomic Analysis in Skeletal Muscle of C57BL/6 J Mice

2019 ◽  
Vol 150 (2) ◽  
pp. 294-302
Author(s):  
Ya-nan Sun ◽  
Jia-qiang Huang ◽  
Zhong-zhou Chen ◽  
Min Du ◽  
Fa-zheng Ren ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Protein Kinase ◽  
Glucose Metabolism ◽  
Protein Degradation ◽  
Muscle Atrophy ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Serum Glucose ◽  
High Fat

ABSTRACT Background Ectopic fat accumulation in skeletal muscle results in dysfunction and atrophy, but the underlying molecular mechanisms remain unclear. Objective The aim of this study was to investigate the effects of a high-fat diet (HFD) in modulating the structure and energy metabolism of skeletal muscle and the underlying mechanisms in mice. Methods Four-week-old male C57BL/6 J mice (n = 30) were allowed 1 wk for acclimatization. After 6 mice with low body weight were removed from the study, the remaining 24 mice were fed with a normal-fat diet (NFD; 10% energy from fat, n = 12) or an HFD (60% energy from fat, n = 12) for 24 wk. At the end of the experiment, serum glucose and lipid concentrations were measured, and skeletal muscle was collected for atrophy analysis, inflammation measurements, and phosphoproteomic analysis. Results Compared with the NFD, the HFD increased (P &lt; 0.05) body weight (35.8%), serum glucose (64.5%), and lipid (27.3%) concentrations, along with elevated (P &lt; 0.05) expressions of the atrophy-related proteins muscle ring finger 1 (MURF1; 27.6%) and muscle atrophy F-box (MAFBX; 44.5%) in skeletal muscle. Phosphoproteomic analysis illustrated 64 proteins with differential degrees of phosphorylation between the HFD and NFD groups. These proteins were mainly involved in modulating cytoskeleton [adenylyl cyclase-associated protein 2 (CAP2) and actin-α skeletal muscle (ACTA1)], inflammation [NF-κB-activating protein (NKAP) and serine/threonine-protein kinase RIO3 (RIOK3)], glucose metabolism [Cdc42-interacting protein 4 (TRIP10); protein kinase C, and casein kinase II substrate protein 3 (PACSIN3)], and protein degradation [heat shock protein 90 kDa (HSP90AA1)]. The HFD-induced inhibitions of the insulin signaling pathway and activations of inflammation in skeletal muscle were verified by Western blot analysis. Conclusions Quantitative phosphoproteomic analysis in C57BL/6 J mice fed an NFD or HFD for 24 wk revealed that the phosphorylation of inflammatory proteins and proteins associated with glucose metabolism at specific serine residues may play critical roles in the regulation of skeletal muscle atrophy induced by an HFD. This work provides information regarding underlying molecular mechanisms for inflammation-induced dysfunction and atrophy in skeletal muscle.

Adiponectin is required to mediate rimonabant-induced improvement of insulin sensitivity but not body weight loss in diet-induced obese mice

2009 ◽  
Vol 296 (4) ◽  
pp. R929-R935 ◽  
Author(s):  
Stéphanie Migrenne ◽  
Amélie Lacombe ◽  
Anne-Laure Lefèvre ◽  
Marie-Pierre Pruniaux ◽  
Etienne Guillot ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Energy Homeostasis ◽  
Hepatic Glucose Production ◽  
Body Weight Loss ◽  
Metabolic Effects ◽  
Wild Type ◽  
High Fat ◽  
Wild Type Littermate

The increase in adiponectin levels in obese patients with untreated dyslipidemia and its mRNA expression in adipose tissue of obese animals are one of the most interesting consequences of rimonabant treatment. Thus, part of rimonabant's metabolic effects could be related to an enhancement of adiponectin secretion and its consequence on the modulation of insulin action, as well as energy homeostasis. The present study investigated the effects of rimonabant in adiponectin knockout mice (Ad−/−) exposed to diet-induced obesity conditions. Six-week-old Ad−/− male mice and their wild-type littermate controls (Ad+/+) were fed a high-fat diet for 7 mo. During the last month, animals were administered daily either with vehicle or rimonabant by mouth (10 mg/kg). High-fat feeding induced weight gain by about 130% in both wild-type and Ad−/− mice. Obesity was associated with hyperinsulinemia and insulin resistance. Treatment with rimonabant led to a significant and similar decrease in body weight in both Ad+/+ and Ad−/− mice compared with vehicle-treated animals. In addition, rimonabant significantly improved insulin sensitivity in Ad+/+ mice compared with Ad+/+ vehicle-treated mice by decreasing hepatic glucose production and increasing glucose utilization index in both visceral and subcutaneous adipose tissue. In contrast, rimonabant failed to improve insulin sensitivity in Ad−/− mice, despite the loss in body weight. Rimonabant's effect on body weight appeared independent of the adiponectin pathway, whereas adiponectin seems required to mediate rimonabant-induced improvement of insulin sensitivity in rodents.

scholarly journals A COMPARATIVE EVALUATION OF ANTI-DIABETIC POTENTIALITY FOUND IN DIFFERENT MARKETED POLYHERBAL FORMULATION USING GLUCOCORTICOID-INDUCED HYPERGLYCAEMIA IN RABBIT

2017 ◽  
Vol 9 (4) ◽  
pp. 83
Author(s):  
Pranjal Boruah ◽  
Jashabir Chakraborty ◽  
Suvakanta Dash
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Blood Glucose ◽  
Normal Saline ◽  
Side Effect ◽  
Body Weight Loss ◽  
Control Group ◽  
Therapeutic Equivalence ◽  
Polyherbal Formulation ◽  
Single Dosage

Objective: The aim of this study was performed to evaluate Antidiabetic potentiality found in different marketed polyherbal formulation using glucocorticoid-induced hyperglycaemia in the rabbit.Methods: The potentiality of different polyherbal formulation was investigated using dexamethasone (DEX) induced hyperglycaemia in Rabbit. Eight male rabbits were divided into four groups of two each. The first group is regarded as control group received 3 ml of normal saline daily by using the gastric tube for 15 d and remaining three group received (0.35 mg/Kg B.W. single dosage) of dexamethasone tablets which were powdered, dissolved in 3 ml of normal saline daily for 15 d. After 15 d the blood glucose estimated by using a glucometer and it is found that DXE treatment leads to significant increase in levels of glucose and a significant decrease in body weight. After that second group received metformin tablet. The third and fourth group received polyherbal formulation A and formulation B, which are powdered and dissolved in 3 ml of normal saline daily for 15 d at the dose of 0.5 gm/kg body weight orally. After completion of regular administration for 15 d, the blood glucose was again estimated and compare the results of each the group.Conclusion: The Anti-diabetic polyherbal marketed formulations were having less side effect as compared to standard metformin tablet (e. g. body weight loss). And both the polyherbal formulations were found a therapeutic equivalence to each other, also having the approximately similar potentiality to standard metformin tablet.Results: The result was found that the polyherbal marketed formulations were having less side effect as compared to standard metformin tablet (e. g. body weight loss). And both the polyherbal formulations were found significantly decreased in blood glucose level at equal potentiality, which can be consider as therapeutic equivalence to each other, and both the formulation also having the approximately similar potentiality to standard metformin tablet. 

Sign in / Sign up

Export Citation Format

Share Document