scholarly journals The key role of a glucagon-like peptide-1 receptor agonist in body fat redistribution

2019 ◽  
Vol 240 (2) ◽  
pp. 271-286 ◽  
Author(s):  
Li Zhao ◽  
Chunfang Zhu ◽  
Meng Lu ◽  
Chi Chen ◽  
Xiaomin Nie ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Body Fat ◽  
Visceral Fat ◽  
Subcutaneous Fat ◽  
Control Group ◽  
Acid Oxidation ◽  
High Dose ◽  
Fat Depots ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an ideal therapy for type 2 diabetes and, as of recently, for obesity. In contrast to visceral fat, subcutaneous fat appears to be protective against metabolic diseases. Here, we aimed to explore whether liraglutide, a GLP-1RA, could redistribute body fat via regulating lipid metabolism in different fat depots. After being fed a high-fat diet for 8 weeks, 50 male Wistar and Goto-Kakizaki rats were randomly divided into a normal control group, a diabetic control group, low- and high-dose liraglutide-treated groups and a diet-control group. Different doses of liraglutide (400 μg/kg/day or 1200 μg/kg/day) or an equal volume of normal saline were administered to the rats subcutaneously once a day for 12 weeks. Body composition and body fat deposition were measured by dual-energy X-ray absorptiometry and MRI. Isotope tracers were infused to explore lipid metabolism in different fat depots. Quantitative real-time PCR and Western blot analyses were conducted to evaluate the expression of adipose-related genes. The results showed that liraglutide decreased visceral fat and relatively increased subcutaneous fat. Lipogenesis was reduced in visceral white adipose tissue (WAT) but was elevated in subcutaneous WAT. Lipolysis was also attenuated, and fatty acid oxidation was enhanced. The mRNA expression levels of adipose-related genes in different tissues displayed similar trends after liraglutide treatment. In addition, the expression of browning-related genes was upregulated in subcutaneous WAT. Taken together, the results suggested that liraglutide potentially redistributes body fat and promotes browning remodeling in subcutaneous WAT to improve metabolic disorders.

scholarly journals Lipid metabolism in women

2004 ◽  
Vol 63 (1) ◽  
pp. 153-160 ◽  
Author(s):  
Christine M. Williams
Keyword(s):  
Adipose Tissue ◽  
Cardiovascular Risk ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Body Fat ◽  
Adrenergic Receptors ◽  
Subcutaneous Fat ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Fat Depots

Differences in whole-body lipid metabolism between men and women are indicated by lower-body fat accumulation in women but more marked accumulation of fat in the intra-abdominal visceral fat depots of men. Circulating blood lipid concentrations also show gender-related differences. These differences are most marked in premenopausal women, in whom total cholesterol, LDL-cholesterol and triacylglycerol concentrations are lower and HDL-cholesterol concentration is higher than in men. Tendency to accumulate body fat in intra-abdominal fat stores is linked to increased risk of CVD, metabolic syndrome, diabetes and other insulin-resistant states. Differential regional regulation of adipose tissue lipolysis and lipogenesis must underlie gender-related differences in the tendency to accumulate fat in specific fat depots. However, empirical data to support current hypotheses remain limited at the present time because of the demanding and specialist nature of the methods used to study adipose tissue metabolism in human subjects. In vitro and in vivo data show greater lipolytic sensitivity of abdominal subcutaneous fat and lesser lipolytic sensitivity of femoral and gluteal subcutaneous fat in women than in men. These differences appear to be due to fewer inhibitory α adrenergic receptors in abdominal regions and greater α adrenergic receptors in gluteal and femoral regions in women than in men. There do not appear to be major gender-related differences in rates of fatty acid uptake (lipogenesis) in different subcutaneous adipose tissue regions. In visceral fat rates of both lipolysis and lipogenesis appear to be greater in men than in women; higher rates of lipolysis may be due to fewer α adrenergic receptors in this fat depot in men. Fatty acid uptake into this depot in the postprandial period is approximately 7-fold higher in men than in women. Triacylglycerol concentrations appear to be a stronger cardiovascular risk factor in women than in men, with particular implications for cardiovascular risk in diabetic women. The increased triacylglycerol concentrations observed in women taking hormone-replacement therapy (HRT) may explain the paradoxical findings of increased rates of CVD in women taking HRT that have been reported from recent primary and secondary prevention trials of HRT.

Hyperleptinemia: an early sign of juvenile obesity. Relations to body fat depots and insulin concentrations

1996 ◽  
Vol 271 (3) ◽  
pp. E626-E630 ◽  
Author(s):  
S. Caprio ◽  
W. V. Tamborlane ◽  
D. Silver ◽  
C. Robinson ◽  
R. Leibel ◽  
...  
Keyword(s):  
Body Fat ◽  
Fat Mass ◽  
Visceral Fat ◽  
Subcutaneous Fat ◽  
Ventromedial Hypothalamus ◽  
Strong Positive Correlation ◽  
Fat Depots ◽  
Hyperglycemic Clamp ◽  
Juvenile Obesity ◽  
Fat Depot

Leptin, the OB gene product, is an adipocyte-derived circulating protein. In several rodent models of obesity, such as the db/db mice, fa/fa rats, and ventromedial hypothalamus-lesioned mice, as well as adult obese subjects, leptin mRNA expression and the circulating levels are elevated, suggesting resistance to its action. However, it is unknown whether the rise in leptin concentration occurs early in the natural evolution of human obesity or is a chronic adaptation to the obese state. Moreover, whether the distribution of body fat (i.e., visceral vs. subcutaneous abdominal fat) influences circulating leptin levels has not been assessed. We have determined in a group of obese and nonobese children and young adults whether leptin levels 1) are increased early in the development of obesity, 2) are related to a specific fat depot measured by magnetic resonance imaging, 3) vary during hyperinsulinemic, euglycemic, and hyperglycemic clamp studies, and 4) are different in males vs. females. In the basal state, leptin levels were elevated in obese children. Children and adults demonstrated a strong positive correlation between leptin concentrations and the subcutaneous fat depot (r = 0.84, P < 0.001). Surprisingly, a weaker correlation was found with visceral fat mass (r = 0.59, P = 0.001). Leptin levels remained unchanged under both euglycemic and hyperglycemic hyperinsulinemic conditions in both obese and nonobese subjects. A pronounced effect of gender on leptin levels was also observed. We conclude that, early in the development of juvenile obesity, leptin concentrations are elevated and are more closely linked to subcutaneous than visceral fat mass. Acute increases in insulin concentrations do not affect circulating leptin levels.

1019-P: Glucagon-Like Peptide-1 Receptor Agonists Predominantly Reduce Body Fat Mass in Patients with Type 2 Diabetes

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1019-P
Author(s):  
YUKI FUJITA ◽  
SODAI KUBOTA ◽  
HITOSHI KUWATA ◽  
DAISUKE YABE ◽  
YOSHIYUKI HAMAMOTO ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Fat ◽  
Fat Mass ◽  
Body Fat Mass ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Nitrergic contribution to gastric relaxation induced by glucagon-like peptide-1 (GLP-1) in healthy adults

2007 ◽  
Vol 292 (5) ◽  
pp. G1359-G1365 ◽  
Author(s):  
Christopher N. Andrews ◽  
Adil E. Bharucha ◽  
Michael Camilleri ◽  
Phillip A. Low ◽  
Barbara Seide ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Low Dose ◽  
Photon Emission ◽  
Gastric Volume ◽  
Emission Computed Tomography ◽  
High Dose ◽  
Double Blind Study ◽  
Vagal Activity ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The incretin glucagon-like peptide-1 (GLP-1), which is used to treat diabetes mellitus, delays gastric emptying by inhibiting vagal activity. GLP-1 also increases fasting and postprandial gastric volume in humans. On the basis of animal studies, we hypothesized that nitric oxide mediates the effects of GLP-1 on gastric volumes. To assess the effects of nitrergic blockade on GLP-1-induced gastric accommodation in humans, in this double-blind study, 31 healthy volunteers were randomized to placebo (i.e., saline), GLP-1, or the nitric oxide synthase inhibitor NG-monomethyl-l-arginine acetate (l-NMMA; 4 mg·kg−1·h−1) alone or with GLP-1. Thereafter, 16 additional subjects were randomized to GLP-1 alone or together with a higher dose of l-NMMA (10 mg/kg bolus plus 8 mg·kg−1·h−1 infusion). Gastric volumes (fasting pre- and postdrug, postprandial postdrug) were measured by 99mTc-single-photon-emission computed tomography imaging. GLP-1 increased ( P = 0.04) fasting gastric volume by 83 ± 16 ml (vs. 17 ± 11 ml for placebo) and augmented ( P ≤ 0.01) postprandial accommodation by 688 ± 165 ml (vs. 542 ± 29 ml for placebo). l-NMMA (low dose) alone did not affect fasting or postprandial gastric volume. l-NMMA (low dose) did not attenuate the effect of GLP-1 on gastric volumes. In contrast, l-NMMA (high dose) did not affect fasting volume but blunted GLP-1-mediated postprandial accommodation (postprandial change = 494 ± 37 ml, P ≤ 0.01 vs. GLP-1 alone). These data are consistent with the hypothesis that nitric oxide partly mediates the effects of GLP-1 on postprandial but not fasting gastric volumes in humans.

Effect of intraportal glucagon-like peptide-1 on glucose metabolism in conscious dogs

2003 ◽  
Vol 284 (5) ◽  
pp. E1027-E1036 ◽  
Author(s):  
Makoto Nishizawa ◽  
Mary Courtney Moore ◽  
Masakazu Shiota ◽  
Stephanie M. Gustavson ◽  
Wanda L. Snead ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Conscious Dogs ◽  
Glucose Disposal ◽  
Control Group ◽  
Hepatic Glucose ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Hepatic Glucose Uptake ◽  
Arteriovenous Difference ◽  
Intraportal Infusion

Arteriovenous difference and tracer ([3-3H]glucose) techniques were used in 42-h-fasted conscious dogs to identify any insulin-like effects of intraportally administered glucagon-like peptide 1-(7–36)amide (GLP-1). Each study consisted of an equilibration, a basal, and three 90-min test periods (P1, P2, and P3) during which somatostatin, intraportal insulin (3-fold basal) and glucagon (basal), and peripheral glucose were infused. Saline was infused intraportally in P1. During P2 and P3, GLP-1 was infused intraportally at 0.9 and 5.1 pmol · kg−1 · min−1in eight dogs, at 10 and 20 pmol · kg−1 · min−1in seven dogs, and at 0 pmol · kg−1 · min−1in eight dogs (control group). Net hepatic glucose uptake was significantly enhanced during GLP-1 infusion at 20 pmol · kg−1 · min−1[21.8 vs. 13.4 μmol · kg−1 · min−1(control), P < 0.05]. Glucose utilization was significantly increased during infusion at 10 and 20 pmol · kg−1 · min−1[87.3 ± 8.3 and 105.3 ± 12.8, respectively, vs. 62.2 ± 5.3 and 74.7 ± 7.4 μmol · kg−1 · min−1(control), P < 0.05]. The glucose infusion rate required to maintain hyperglycemia was increased ( P < 0.05) during infusion of GLP-1 at 5.1, 10, and 20 pmol · kg−1 · min−1(22, 36, and 32%, respectively, greater than control). Nonhepatic glucose uptake increased significantly during delivery of GLP-1 at 5.1 and 10 pmol · kg−1 · min−1(25 and 46% greater than control) and tended ( P = 0.1) to increase during GLP-1 infusion at 20 pmol · kg−1 · min−1(24% greater than control). Intraportal infusion of GLP-1 at high physiological and pharmacological rates increased glucose disposal primarily in nonhepatic tissues.

scholarly journals Human Epicardial Fat Expresses Glucagon-Like Peptide 1 and 2 Receptors Genes

2017 ◽  
Vol 49 (08) ◽  
pp. 625-630 ◽  
Author(s):  
Gianluca Iacobellis ◽  
Vladimir Camarena ◽  
David Sant ◽  
Gaofeng Wang
Keyword(s):  
Subcutaneous Fat ◽  
Metabolic Effects ◽  
Pcr Analysis ◽  
Rna Seq ◽  
Elective Cardiac Surgery ◽  
Qrt Pcr ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Artery Disease ◽  
Successful Amplification

AbstractEpicardial adipose tissue (EAT) is an easily measurable visceral fat of the heart with unique anatomy, functionality, and transcriptome. EAT can serve as a therapeutic target for pharmaceutical agents targeting the fat. Glucagon-like peptide-1 (GLP-1) and GLP-2 analogues are newer drugs showing beneficial cardiovascular and metabolic effects. Whether EAT expresses GLP- 1 and 2 receptors (GLP-1R and GLP-2R) is unknown. RNA-seq analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to evaluate the presence of GLP-1R and GLP-2R in EAT and subcutaneous fat (SAT) obtained from 8 subjects with coronary artery disease and type 2 diabetes mellitus undergoing elective cardiac surgery. Immunofluorescence was also performed on EAT and SAT samples using Mab3f52 against GLP-1R. Our RNA-sequencing (RNA-seq) analysis showed that EAT expresses both GLP-1R and GLP-2R genes. qRT-PCR analysis confirmed that GLP-1R expression was low but detected by 2 different sets of intron-spanning primers. GLP-2R expression was detected in all patients and was found to be 5-fold higher than GLP-1R. The combination of accurately spliced reads from RNA-seq and successful amplification using intron-spanning primers indicates that both GLP-1R and GLP-2R are expressed in EAT. Immunofluorescence clearly showed that GLP-1R is present and more abundant in EAT than SAT. This is the first time that human EAT is found to express both GLP-1R and GLP-2R genes. Pharmacologically targeting EAT may induce beneficial cardiovascular and metabolic effects.

scholarly journals Glucagon-Like Peptide-1 (GLP-1) Reduces Mortality and Improves Lung Function in a Model of Experimental Obstructive Lung Disease in Female Mice

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4503-4511 ◽  
Author(s):  
Niels-Erik Viby ◽  
Marie S. Isidor ◽  
Katrine B. Buggeskov ◽  
Steen S. Poulsen ◽  
Jacob B. Hansen ◽  
...  
Keyword(s):  
Lung Function ◽  
Lung Disease ◽  
Obstructive Lung Disease ◽  
Whole Body ◽  
Control Group ◽  
Chronic Obstructive ◽  
Mrna Levels ◽  
Female Mice ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The incretin hormone glucagon-like peptide-1 (GLP-1) is an important insulin secretagogue and GLP-1 analogs are used for the treatment of type 2 diabetes. GLP-1 displays antiinflammatory and surfactant-releasing effects. Thus, we hypothesize that treatment with GLP-1 analogs will improve pulmonary function in a mouse model of obstructive lung disease. Female mice were sensitized with injected ovalbumin and treated with GLP-1 receptor (GLP-1R) agonists. Exacerbation was induced with inhalations of ovalbumin and lipopolysaccharide. Lung function was evaluated with a measurement of enhanced pause in a whole-body plethysmograph. mRNA levels of GLP-1R, surfactants (SFTPs), and a number of inflammatory markers were measured. GLP-1R was highly expressed in lung tissue. Mice treated with GLP-1R agonists had a noticeably better clinical appearance than the control group. Enhanced pause increased dramatically at day 17 in all control mice, but the increase was significantly less in the groups of GLP-1R agonist-treated mice (P &lt; .001). Survival proportions were significantly increased in GLP-1R agonist-treated mice (P &lt; .01). SFTPB and SFTPA were down-regulated and the expression of inflammatory cytokines were increased in mice with obstructive lung disease, but levels were largely unaffected by GLP-1R agonist treatment. These results show that GLP-1R agonists have potential therapeutic potential in the treatment of obstructive pulmonary diseases, such as chronic obstructive pulmonary disease, by decreasing the severity of acute exacerbations. The mechanism of action does not seem to be the modulation of inflammation and SFTP expression.

scholarly journals Supplementation of Low Ratio n-6:n-3 PUFA Reduces Body Fatness in Young Obese Balinese Women: A Randomized Study with Optimized Energy Regulation

2020 ◽  
pp. 584-595
Author(s):  
I Wayan Weta ◽  
Wayan P Sutirtayasa ◽  
Wayan C Sucipta ◽  
Safarina G Malik ◽  
A.A.Ngurah Subawa ◽  
...  
Keyword(s):  
Energy Intake ◽  
Body Fat ◽  
Randomized Study ◽  
Intervention Group ◽  
Control Group ◽  
High Dose ◽  
Energy Regulation ◽  
Body Fatness ◽  
Alcoholic Fatty Liver ◽  
Conicity Index

Background and Objectives: Obese Indonesians, including Balinese, are at higher risk of comorbidities like, CVD, diabetes, non-alcoholic fatty liver disease. Urban Balinese are changing their diet from traditional to fast foods and the like that are high in saturated fats. Nutritional modification, such as increasing n-3 PUFA content in the diet, may aid in managing body fat accumulation-related diseases. This study investigated the effects of supplementation of n-6:n-3 PUFA with ratio of 2:1 on body fat reduction in young obese Balinese women. Methods and Study Design: Sixty-six young obese Balinese women, aged 18-25, were randomly assigned equally into Intervention and Control groups, supplemented with 2100 mg:1100 mg and 240 mg:100 mg of n-6:n-3 PUFAs, respectively. Data were collected at baseline, 6, and 12 weeks of intervention. BMI, waist circumference (WC), waist-to-height ratio (WHtR), conicity index, triglyceride concentrations, and Lipid Accumulation Product (LAP) were measured. Participants were advised to maintain <1500-Kcal daily energy intake and participate in a guided low-impact aerobics once a week. Results: After 12-weeks supplementation, all body fat indices (BMI, WC, WHtR, conicity index, and LAP), decreased significantly weather were unadjusted or adjusted by the reduced of energy intake in the Intervention group. Otherwise, in the Control group only some of WC indices (WC, WHtR, and conicity index) decreased stasticically. BMI and WC of the Intervention group decreased significantly more than the Control group. Conclusion: Twelve-week intervention with high-dose of low n-6:n-3 PUFAs ratio and restriction energy intake, reduced body fatness selectively in young obese Balinese women.

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