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

Zhao, Li; Zhu, Chunfang; Lü, Meng; Chen, Chi; Nie, Xiaomin; Abudukerimu, Buatikamu; Zhang, Kun; Zhang, Ning; Chen, Yi; Cheng, Jing; Xia, Fangzhen; Wang, Ningjian; Jensen, Michael D.; Lu, Yingli

doi:10.1530/joe-18-0374

Cited by 36 publications

(24 citation statements)

References 52 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Liraglutide has also been shown to reduce total body fat and to increase fat free mass in type 2 diabetes in one study 11 . Based on observations in animals, it is suggested that GLP‐1 receptor agonists increase energy expenditure through increased lipid oxidation and thermogenesis 11,12 . In animals and in morbidly obese patients, GLP‐1 receptor expression has been shown to increase in proportion to the co‐existent insulin resistance 13 .…”

Section: Discussionmentioning

confidence: 99%

“…11 Based on observations in animals, it is suggested that GLP-1 receptor agonists increase energy expenditure through increased lipid oxidation and thermogenesis. 11,12 In animals and in morbidly obese patients, GLP-1 receptor expression has been shown to increase in proportion to the co-existent insulin resistance. 13 However, there are no previous data on the loss of body fat in association with the preservation of lean body mass following liraglutide in patients with T1DM.…”

Section: Changes In Glucagon Incretins and Meal Responsementioning

confidence: 99%

See 1 more Smart Citation

Liraglutide treatment in overweight and obese patients with type 1 diabetes: A 26‐week randomized controlled trial; mechanisms of weight loss

Ghanim

Batra

Green

et al. 2020

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

Aim To investigate the effects of liraglutide treatment on glycaemic control and adipose tissue metabolism in overweight and obese people with type 1 diabetes (T1DM). Research design and methods A total of 84 adult overweight and obese patients with T1DM, with no detectable C‐peptide, were randomized (1:1) to either placebo or 1.8 mg/d liraglutide for 6 months. Blood samples were collected at 0, 12 and 26 weeks. Subcutaneous adipose tissue biopsies, a high‐calorie high‐fat meal challenge test, continuous glucose monitoring, dual‐energy X‐ray absorptiometry and MRI were performed before and at the end of treatment. Results In all, 37 and 27 patients who received liraglutide and placebo, respectively, completed the study. Glycated haemoglobin fell by 0.41 ± 0.18% (4.5±1.4 mmol/mol) from baseline after liraglutide treatment (P = 0.001), and by 0.29 ± 0.19% (3.1±2.0 mmol/mol) compared to placebo (P = 0.1). There was no increase in hypoglycaemia, while the time spent in normal glycaemia increased (P = 0.015) and time spent in hyperglycaemia decreased (P = 0.019). Body weight fell significantly in the liraglutide group, mostly in the form of fat mass loss (including visceral fat), with no change in lean mass. Systolic blood pressure (SBP) also fell after liraglutide treatment. Liraglutide also caused a significant increase in the expression of adipose tissue triglyceride lipase, carnitine palmitoyl transferase‐1, peroxisome proliferator‐activated receptor (PPAR)α, PPARδ, uncoupling protein‐2 and type 2 iodothyronine deiodinase in the adipose tissue. Conclusions Liraglutide improves glycaemia, reduces adiposity and SBP. Liraglutide also stimulates mechanisms involved with an increase in lipid oxidation and thermogenesis, while conserving lean body mass.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Changes In Glucagon Incretins and Meal Responsementioning

confidence: 99%

Liraglutide treatment in overweight and obese patients with type 1 diabetes: A 26‐week randomized controlled trial; mechanisms of weight loss

Ghanim

Batra

Green

et al. 2020

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

show abstract

“…Recently, GLP-1 RAs have been used as a preferred treatment for patients with diabetes and obesity [26,27]. Previous studies have suggested that liraglutide can play a hypoglycemic role by increasing insulin secretion, improving islet cell function and reducing body weight in diabetic mice and obese rats [28][29][30]. Others also con rmed that GLP-1 RAs inhibited the formation of lipid droplets in different cells lines [31,32].…”

Section: Discussionmentioning

confidence: 99%

The Novel Hepatokine Ectodysplasin A Is Increased in Obesity and Reduced after Liraglutide Management

Cai

Deng

Zhang

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Background Ectodysplasin A (EDA), a new hepatokine, has been recently characterized to play a role in liver lipid metabolism and insulin resistance, but its physiological role remains scarcely acquainted in obesity. This study was the first time to determine the level of serum EDA in obesity, and to assess change in the levels of EDA after weight loss in obese mice.Methods We analyzed the serum concentrations of EDA by enzyme-linked immunosorbent assay (ELISA) in 60 subjects including 30 normal weight and 30 obesity. Male C57BL/6J mice were fed with high-fat diet and injected by liraglutide to reduce weight. AML12 cells were induced by palmitic acid and treated with liraglutide. Quantitative real-time PCR and Western blot analysis were conducted to evaluate the expression of EDA. Results Serum EDA levels were significantly higher in obesity than in normal weight subjects. It was positively correlated with body mass index (BMI). More importantly, the mRNA and protein expression of EDA reduced after liraglutide management in vivo and in vitro.Conclusions The level of EDA increased significantly in obesity and decreased significantly after weight loss. It is suggested that EDA may be a novel hepatokine associated with obesity-related metabolic diseases.

show abstract

“…It has previously been shown that GLP-1 increases the expression of lipolytic markers while reducing expression of lipogenic and adipogenic genes in adipose tissue, with distinct effects on subcutaneous and visceral adipose tissue [40]. In another study, expression of brown adipose tissuerelated genes was upregulated in subcutaneous adipose tissue of rats after treatment with liraglutide [41]. In line, it was recently shown that liraglutide-induced weight reduction resulted in a greater reduction of visceral adipose tissue volume than lifestyle counselling at similar weight reduction [42].…”

Section: Characteristicmentioning

confidence: 90%

A double-blind, placebo-controlled, randomised trial to assess the effect of liraglutide on ectopic fat accumulation in South Asian type 2 diabetes patients

Eyk

Paiman

Bizino

et al. 2019

Cardiovasc Diabetol

View full text Add to dashboard Cite

Background South Asians have a high risk to develop type 2 diabetes, which may be related to substantial ectopic fat deposition. Since glucagon-like peptide-1 analogues can reduce ectopic fat accumulation, the aim of the present study was to assess the effect of treatment with liraglutide for 26 weeks on ectopic fat deposition and HbA1c in South Asian patients with type 2 diabetes. Methods In a placebo-controlled trial, 47 South Asian patients with type 2 diabetes were randomly assigned to treatment with liraglutide (1.8 mg/day) or placebo added to standard care. At baseline and after 26 weeks of treatment we assessed abdominal subcutaneous, visceral, epicardial and paracardial adipose tissue volume using MRI. Furthermore, myocardial and hepatic triglyceride content were examined with proton magnetic resonance spectroscopy. Results In the intention-to-treat analysis, liraglutide decreased body weight compared to placebo (− 3.9 ± 3.6 kg vs − 0.6 ± 2.2 kg; mean change from baseline (liraglutide vs placebo): − 3.5 kg; 95% CI [− 5.3, − 1.8]) without significant effects on the different adipose tissue compartments. HbA1c was decreased in both groups without between group differences. In the per-protocol analysis, liraglutide did decrease visceral adipose tissue volume compared to placebo (− 23 ± 27 cm 2 vs − 2 ± 17 cm 2 ; mean change from baseline (liraglutide vs placebo): − 17 cm 2 ; 95% CI [− 32, − 3]). Furthermore, HbA1c was decreased by liraglutide compared to placebo (− 1.0 ± 0.8% (− 10.5 ± 9.1 mmol/mol)) vs (− 0.6 ± 0.8% (− 6.1 ± 8.8 mmol/mol)), with a between group difference (mean change from baseline (liraglutide vs placebo): − 0.6% (− 6.5 mmol/mol); 95% CI [− 1.1, − 0.1 (− 11.5, − 1.5)]). Interestingly, the decrease of visceral adipose tissue volume was associated with the reduction of HbA1c (β: 0.165 mmol/mol (0.015%) per 1 cm 2 decrease of visceral adipose tissue volume; 95% CI [0.062, 0.267 (0.006, 0.024%)]). Conclusions While the intention-to-treat analysis did not show effects of liraglutide on ectopic fat and HbA1c, per-protocol analysis showed that liraglutide decreases visceral adipose tissue volume, which was associated with improved glycaemic control in South Asians. Trial registration NCT02660047 (clinicaltrials.gov). Registered 21 January 2016

show abstract

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

Cited by 36 publications

References 52 publications

Liraglutide treatment in overweight and obese patients with type 1 diabetes: A 26‐week randomized controlled trial; mechanisms of weight loss

Liraglutide treatment in overweight and obese patients with type 1 diabetes: A 26‐week randomized controlled trial; mechanisms of weight loss

The Novel Hepatokine Ectodysplasin A Is Increased in Obesity and Reduced after Liraglutide Management

A double-blind, placebo-controlled, randomised trial to assess the effect of liraglutide on ectopic fat accumulation in South Asian type 2 diabetes patients

Contact Info

Product

Resources

About