Recombinant human GLP-1 beinaglutide regulates lipid metabolism of adipose tissues in diet-induced obese mice

Zhang, Feng; Chen, Zhi‐Nan; Wu, Dan; Liu, Tian; Chen, Qing; Ye, Yuqing; Chen, Wei; Wu, Xiaoxing; Wu, Peng; Yuan, Weilan; Qiu, Yan; Zhou, Zhiguang; Du, Zhiqiang; Hu, Fang

doi:10.1016/j.isci.2021.103382

Cited by 21 publications

(28 citation statements)

References 63 publications

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“…Previous study provided evidence for the presence of GLP-1 receptor in adipose tissue and show that its mRNA and protein expressions increased in visceral adipose depots from morbidly obese patients with a high degree of Insulin resistances (IR) ( 7 ). Interestingly, protein O35659 was not identified by TMT LC-MS in our study, which was consistent with another study of h rhGLP-1 Beinaglutide (BN) on adipose tissue ( 29 ). Potential explanations of this observation may be that the fat loss effect by semaglutide during the course of the experiment, might lower the degree of IR, leading to a lower expression of Glpr in mice, or the beneficial effects of GLP-1 are associated with the activation of not only the canonical GLP-1 receptor but also an additional, as yet unknown, receptor ( 8 ), the effects of semaglutide on adipose tissues might not be through its regulation on expression of GLP-1R.…”

Section: Discussionsupporting

confidence: 93%

“…Recent in vivo evidence has also shown that reducing circulating insulin levels may protect and reverse adiposity, insulin resistance, and hyperglycemia that is associated with obesity ( 28 ). A previous study discovered that plasma fasting insulin and leptin levels decreased in the GLP-1 (rhGLP-1) Beinaglutide (BN) treated mice, suggesting that BN could reduce hyperinsulinemia and hyperleptinemia associated with obesity ( 29 ). Based on the above findings, in this study we indicate that semaglutide could reduce hyperinsulinemia and promote the insulin sensitivity in obese mice.…”

Section: Discussionmentioning

confidence: 99%

“…Second, although the changes of adipose tissue respond to GLP-1 analogues treatment has been studied from the gene expression, lipidomic perspectives ( 29 , 32 ),comprehensive protein level profiling is rare. Gene expression and protein expression diverge ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

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Proteomic analysis reveals semaglutide impacts lipogenic protein expression in epididymal adipose tissue of obese mice

Zhu

Chen

2023

Front. Endocrinol.

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Background and objectivesObesity is a global health problem with few pharmacologic options. Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that induces weight loss. Yet, the role of semaglutide in adipose tissue has not yet been examined. The following study investigated the mechanism of semaglutide on lipid metabolism by analyzing proteomics of epididymal white adipose tissue (eWAT) in obese mice.MethodsA total of 36 C57BL/6JC mice were randomly divided into a normal-chow diet group (NCD, n = 12), high-fat diet (HFD, n = 12), and HFD+semaglutide group (Sema, n = 12). Mice in the Sema group were intraperitoneally administered semaglutide, and the HFD group and the NCD group were intraperitoneally administered an equal volume of normal saline. Serum samples were collected to detect fasting blood glucose and blood lipids. The Intraperitoneal glucose tolerance test (IPGTT) was used to measure the blood glucose value at each time point and calculate the area under the glucose curve. Tandem Mass Tag (TMT) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to study the expression of eWAT, while cellular processes, biological processes, corresponding molecular functions, and related network molecular mechanisms were analyzed by bioinformatics.ResultsCompared with the model group, the semaglutide-treated mice presented 640 differentially expressed proteins (DEPs), including 292 up-regulated and 348 down-regulated proteins. Bioinformatics analysis showed a reduction of CD36, FABP5, ACSL, ACOX3, PLIN2, ANGPTL4, LPL, MGLL, AQP7, and PDK4 involved in the lipid metabolism in the Sema group accompanied by a decrease in visceral fat accumulation, blood lipids, and improvement in glucose intolerance.ConclusionSemaglutide can effectively reduce visceral fat and blood lipids and improve glucose metabolism in obese mice. Semaglutide treatment might have beneficial effects on adipose tissues through the regulation of lipid uptake, lipid storage, and lipolysis in white adipose tissue.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Proteomic analysis reveals semaglutide impacts lipogenic protein expression in epididymal adipose tissue of obese mice

Zhu

Chen

2023

Front. Endocrinol.

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“…The researcher believes that it may be related to the patient’s habit of excessive intake ( 44 ). An animal experiment on mice found that the mechanism of BN treating obesity is targeting the composition of major lipid classes and the expression of genes in lipid metabolism in adipose tissue to counteract high-fat diet-induced obesity ( 45 ).…”

Section: Experimental Evidence Of Glp-1r Agonistsmentioning

confidence: 99%

GLP−1 receptor agonists for the treatment of obesity: Role as a promising approach

Wang

Wang²,

Yang³

et al. 2023

Front. Endocrinol.

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Obesity is a complex disease characterized by excessive fat accumulation which is caused by genetic, environmental and other factors. In recent years, there has been an increase in the morbidity, disability rate,and mortality due to obesity, making it great threat to people’s health and lives, and increasing public health care expenses. Evidence from previous studies show that weight loss can significantly reduce the risk of obesity-related complications and chronic diseases. Diet control, moderate exercise, behavior modification programs, bariatric surgery and prescription drug treatment are the major interventions used to help people lose weight. Among them, anti-obesity drugs have high compliance rates and cause noticeable short-term effects in reducing obese levels. However, given the safety or effectiveness concerns of anti-obesity drugs, many of the currently used drugs have limited clinical use. Glucagon-like peptide-1 receptor (GLP-1R) agonists are a group of drugs that targets incretin hormone action, and its receptors are widely distributed in nerves, islets, heart, lung, skin, and other organs. Several animal experiments and clinical trials have demonstrated that GLP-1R agonists are more effective in treating or preventing obesity. Therefore, GLP-1R agonists are promising agents for the treatment of obese individuals. This review describes evidence from previous research on the effects of GLP-1R agonists on obesity. We anticipate that this review will generate data that will help biomedical researchers or clinical workers develop obesity treatments based on GLP-1R agonists.

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“…8,9 Beinaglutide, a novel recombinant human GLP-1 RA approved for the treatment of Chinese patients with T2D in 2016, 10 is the only prandial GLP-1 RA with a 100% human protein sequence (7-36 GLP-1). [10][11][12] Beinaglutide lowers HbA1c and body weight in patients with T2D and is being recommended by Chinese treatment guidelines as routine clinical practice. 13 The results of small-scale studies suggest that beinaglutide treatment for 12 weeks reduced the body weight of patients with overweight or obesity with 14,15 or without 16 co-morbid diabetes by 5%-10%.…”

Section: Introductionmentioning

confidence: 99%

Beinaglutide for weight management in Chinese individuals with overweight or obesity: A phase 3 randomized controlled clinical study

Chen,

Shan

et al. 2023

Diabetes Obesity Metabolism

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AimTo investigate the efficacy and safety of beinaglutide as an adjunct to lifestyle intervention among non‐diabetic Chinese individuals with overweight or obesity.MethodsThis multicentre, randomized, double‐blind, placebo‐controlled trial (ChiCTR1900023428) included 427 Chinese adults with a body mass index of 28 kg/m2 or higher (obesity) or 24‐27.9 kg/m2 (overweight) with weight‐related complications. Patients were randomized in a 2:1 ratio to receive 0.2 mg of beinaglutide (subcutaneous) thrice daily or placebo for 16 weeks. Co‐primary endpoints were body weight change and the proportion of patients with a weight reduction of 5% or more.ResultsMean body weight change from baseline to week 16 was −6.0% and −2.4% in the beinaglutide (n = 282) and placebo (n = 138) groups, respectively; the mixed model repeated measures difference was −3.6% (95% confidence interval: −4.6% to −2.6%; P < .0001). At week 16, more beinaglutide‐treated patients achieved a weight reduction of 5% or more (58.2% vs. 25.4% [placebo], odds ratio: 4.4; P < .0001) and of 10% or more (21.3% vs. 5.1% [placebo], odds ratio: 5.5; P < .0001). Beinaglutide also resulted in greater waist circumference reduction (difference: −1.81 cm; P < .01). The weight regain rate 12 weeks after beinaglutide treatment was 0.78%. Nausea (transient and mild‐to‐moderate) was the most common adverse event in the beinaglutide group (49.3% vs. 7.1% [placebo]). More patients receiving beinaglutide discontinued treatment because of adverse events (5.9% vs. 0.7% [placebo]). Pancreatitis or an increased resting heart rate was not observed in the beinaglutide group.ConclusionBeinaglutide combined with lifestyle intervention resulted in significant and clinically meaningful weight reduction with good tolerance in non‐diabetic Chinese individuals with overweight or obesity.

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Recombinant human GLP-1 beinaglutide regulates lipid metabolism of adipose tissues in diet-induced obese mice

Cited by 21 publications

References 63 publications

Proteomic analysis reveals semaglutide impacts lipogenic protein expression in epididymal adipose tissue of obese mice

Proteomic analysis reveals semaglutide impacts lipogenic protein expression in epididymal adipose tissue of obese mice

GLP−1 receptor agonists for the treatment of obesity: Role as a promising approach

Beinaglutide for weight management in Chinese individuals with overweight or obesity: A phase 3 randomized controlled clinical study

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