A novel anti-obesity mechanism for liraglutide by improving adipose tissue leptin resistance in high-fat diet-fed obese mice

Lyu, Xiaorui; Yan, Kemin; Wang, Xin; Xu, Hanyuan; Guo, Xiaonan; Zhu, Huijuan; Pan, Hui; Wang, Linjie; Yang, Hongbo; Gong, Fengying

doi:10.1507/endocrj.ej21-0802

Cited by 11 publications

(6 citation statements)

References 54 publications

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“…Liraglutide also promotes a reduction in fat tissue in rodents 28 . Our study revealed a significantly lower adiposity index resulting from reduced retroperitoneal and visceral white adipose tissue depots in high‐dose Liraglutide treatment.…”

Section: Discussionsupporting

confidence: 49%

“…also promotes a reduction in fat tissue in rodents. 28 Our study revealed a significantly lower adiposity index resulting from reduced retroperitoneal and visceral white adipose tissue depots in high-dose Liraglutide treatment. Visceral fat is recognised as an important factor that impacts obesity since this tissue produces inflammatory cytokines and adipokines that worsen metabolic obesity-related diseases.…”

Section: Discussionmentioning

confidence: 49%

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Liraglutide modulates morpho‐functional and inflammatory gastrointestinal responses in rats

Gusmão‐Nascimento,

Nunes Cruz,

Almeida Gama

et al. 2023

Eur J Clin Investigation

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BackgroundObesity impairs homeostatic control of energy and is associated with chronic low‐grade inflammation. Effects of glucagon‐like peptide‐1, the target in the gastrointestinal tract for anti‐obesity drugs such as Liraglutide, were not properly associated with inflammation markers. This study investigated the effects of Liraglutide on metabolic and gastrointestinal parameters in a rat model of obesity.MethodsTwenty‐six Wistar rats with obesity were randomly distributed to receive saline (n = 10), 400 μg (n = 8), or 1200 μg of Liraglutide/kg/day (n = 8), subcutaneously for 30 consecutive days, once a day. Weight gain, feeding efficiency, caloric consumption, gastric motility, adiposity, histomorphometric, murinometric, biochemical parameters and cytokines TNF‐α and TGF‐β1 in duodenal tissue were measured. Data were analysed by ANOVA, followed by Bonferroni post hoc or Kruskal–Wallis test, followed by Dunn's multiple comparison test.ResultsLiraglutide‐treated animals had better feeding efficiency and higher caloric intake in a dose‐dependent manner. Higher doses slowed gastric emptying and diminished the amplitude of gastric contractions. These effects were accompanied by decreases in intestinal muscle layer thickness and crypt depth. Liraglutide significantly reduced retroperitoneal and visceral white adipose tissue depots. High‐dose treatment decreased levels of TNF‐α and enhanced levels of TGF‐β1 in duodenal tissue. Liraglutide treatment provided significant reductions in total cholesterol, triglyceride and hepatic transaminases.ConclusionsLiraglutide reduced fat accumulation, improved metabolic parameters and downregulated levels of inflammatory signalling in duodenal tissue. Liraglutide at high doses controlled obesity‐related outcomes, and such effects seemed to be driven by its action on glucagon‐like peptide‐1 receptors in the gastrointestinal tract slowing gastric motility.

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Section: Discussionsupporting

confidence: 49%

Section: Discussionmentioning

confidence: 49%

Liraglutide modulates morpho‐functional and inflammatory gastrointestinal responses in rats

Gusmão‐Nascimento,

Nunes Cruz,

Almeida Gama

et al. 2023

Eur J Clin Investigation

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“…A decreased concentration of membrane expression of leptin receptors could be associated with impaired leptin sensitivity and, therefore, the pathophysiological state of leptin resistance [39]. Moreover, obesity-related leptin resistance could occur in the hypothalamus, which was named central leptin resistance, while it could also happen in the adipose tissue, liver, and skeletal muscle, which was called peripheral leptin resistance [40]. AMPK-α has been studied for more than two decades as a master regulator of energy balance.…”

Section: Discussionmentioning

confidence: 99%

Dysfunction of the Brown Adipose Organ in HFD-Obese Rats and Effect of Tart Cherry Supplementation

Bellitto,

Gabrielli,

Martinelli

et al. 2024

Antioxidants

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Obesity has a great impact on adipose tissue biology, based on its function as a master regulator of energy balance. Brown adipose tissue (BAT) undergoes remodeling, and its activity declines in obese subjects due to a whitening process. The anti-obesity properties of fruit extracts have been reported. The effects of tart cherry against oxidative stress, inflammation, and the whitening process in the BAT of obese rats were investigated. Intrascapular BAT (iBAT) alterations and effects of Prunus cerasus L. were debated in rats fed for 17 weeks with a high-fat diet (DIO), in DIO supplemented with seed powder (DS), and with seed powder plus the juice (DJS) of tart cherry compared to CHOW rats fed with a normo-caloric diet. iBAT histologic observations revealed a whitening process in DIO rats that was reduced in the DS and DJS groups. A modulation of uncoupling protein-1 (UCP-1) protein and gene expression specifically were detected in the obese phenotype. An upregulation of UCP-1 and related thermogenic genes after tart cherry intake was detected compared to the DIO group. Metabolic adjustment, endoplasmic reticulum stress, protein carbonylation, and the inflammatory microenvironment in the iBAT were reported in DIO rats. The analysis demonstrated an iBAT modulation that tart cherry promoted. In addition to our previous results, these data confirm the protective impact of tart cherry consumption on obesity.

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“…liraglutide 3 mg/day or semaglutide 2.4 mg)/week) are the therapy of choice [93,94]. The cardiometabolic complications of obesity are closely related to adipose tissue dysfunction, and the utility of GLP-1RAs, in this case, is justified by their favourable impact on the metabolic inflammation and restoration of normal adipokine secretion and action, including downregulation of resistin, TNF-a, IL-1b, and IL-6 serum level with a parallel increase in adiponectin concentrations and leptin sensitivity [95,96,97]. The abovementioned GLP-1RAs introduced changes that translate also to the improved function of the endocrine system.…”

Section: Pharmacological Treatmentmentioning

confidence: 99%

Adipose tissue as a cause of endocrine dysfunction

Kuryłowicz

2023

Endokrynol Pol

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The role of adipose tissue in hormonal homeostasisResearch over the past 20 years has changed our understanding of the role of adipose tissue in maintaining the body's homeostasis. It is no longer perceived solely as an energy store, but also as a secretory organ that produces substances (adipokines) that affect the functioning of other organs and tissues [1]. At the same time, adipose tissue is the site of synthesis and metabolism of several steroid hormones, which are released into the bloodstream and contribute to the pool of endogenous steroids [2]. The proper functioning of the endocrine system is determined by signals received from adipose tissue and by normal steroid hormone metabolism in adipocytes. The effect of secretory activity of adipose tissue on endocrine gland functionThe hypothalamic-pituitary-insulin-like growth factor 1 axis The adipokine best studied for its modulatory effect on the hypothalamic-pituitary-insulin-like growth factor 1

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A novel anti-obesity mechanism for liraglutide by improving adipose tissue leptin resistance in high-fat diet-fed obese mice

Cited by 11 publications

References 54 publications

Liraglutide modulates morpho‐functional and inflammatory gastrointestinal responses in rats

Liraglutide modulates morpho‐functional and inflammatory gastrointestinal responses in rats

Dysfunction of the Brown Adipose Organ in HFD-Obese Rats and Effect of Tart Cherry Supplementation

Adipose tissue as a cause of endocrine dysfunction

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