Dataset Information

Effects of colchicine on lipolysis and adipose tissue inflammation in adults with obesity and metabolic syndrome.

ABSTRACT:

Objective

The aim of this study was to examine whether colchicine's anti-inflammatory effects would improve measures of lipolysis and distribution of leukocyte populations in subcutaneous adipose tissue (SAT).

Methods

A secondary analysis was conducted for a double-blind, randomized, placebo-controlled pilot study in which 40 adults with obesity and metabolic syndrome (MetS) were randomized to colchicine 0.6 mg or placebo twice daily for 3 months. Non-insulin-suppressible (l₀ ), insulin-suppressible (l₂ ), and maximal (l₀ +l₂ ) lipolysis rates were calculated by minimal model analysis. Body composition was determined by dual-energy x-ray absorptiometry. SAT leukocyte populations were characterized by flow cytometry analysis from biopsied samples obtained before and after the intervention.

Results

Colchicine treatment significantly decreased l₂ and l₀ +l₂ versus placebo (p < 0.05). These changes were associated with a significant reduction in markers of systemic inflammation, including high-sensitivity C-reactive protein, resistin, and circulating monocytes and neutrophils (p < 0.01). Colchicine did not significantly alter SAT leukocyte population distributions (p > 0.05).

Conclusions

In adults with obesity and MetS, colchicine appears to improve insulin regulation of lipolysis and reduce markers of systemic inflammation independent of an effect on local leukocyte distributions in SAT. Further studies are needed to better understand the mechanisms by which colchicine affects adipose tissue metabolic pathways in adults with obesity and MetS.

SUBMITTER: Levine JA

PROVIDER: S-EPMC8799499 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Effects of colchicine on lipolysis and adipose tissue inflammation in adults with obesity and metabolic syndrome.

Levine Jordan A JA Sarrafan-Chaharsoughi Zahra Z Patel Tushar P TP Brady Sheila M SM Chivukula K Karthik KK Miller Emily E Han Jung Min JM Periwal Vipul V Wolska Anna A Remaley Alan T AT Dagur Pradeep K PK Biancotto Angelique A Babyak Ashley A Fantoni Giovanna G Yanovski Jack A JA Demidowich Andrew P AP

Obesity (Silver Spring, Md.) 20220103 2

<h4>Objective</h4>The aim of this study was to examine whether colchicine's anti-inflammatory effects would improve measures of lipolysis and distribution of leukocyte populations in subcutaneous adipose tissue (SAT).<h4>Methods</h4>A secondary analysis was conducted for a double-blind, randomized, placebo-controlled pilot study in which 40 adults with obesity and metabolic syndrome (MetS) were randomized to colchicine 0.6 mg or placebo twice daily for 3 months. Non-insulin-suppressible (l<sub>0 ...[more]

PMID: 34978374

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Project description:ObjectiveThe worldwide prevalence of obesity has increased to 10% in men and 15% in women and is associated with severe comorbidities such as diabetes, cancer, and cardiovascular disease. Animal models of obesity are central to experimental studies of disease mechanisms and therapeutic strategies. Diet-induced obesity (DIO) models in rodents have provided important insights into the pathophysiology of obesity and, in most instances, are the first in line for exploratory pharmacology studies. To deepen the relevance towards translation to human patients, we established a corresponding DIO model in Göttingen minipigs (GM).MethodsYoung adult female ovariectomized GM were fed a high-fat/high-energy diet for a period of 70 weeks. The ration was calculated to meet the requirements and maintain body weight (BW) of lean adult minipigs (L-GM group) or increased stepwise to achieve an obese state (DIO-GM group). Body composition, blood parameters and intravenous glucose tolerance were determined at regular intervals. A pilot chronic treatment trial with a GLP1 receptor agonist was conducted in DIO-GM. At the end of the study, the animals were necropsied and a biobank of selected tissues was established.ResultsDIO-GM developed severe subcutaneous and visceral adiposity (body fat >50% of body mass vs. 22% in L-GM), increased plasma cholesterol, triglyceride, and free fatty acid levels, insulin resistance (HOMA-IR >5 vs. 2 in L-GM), impaired glucose tolerance and increased heart rate when resting and active. However, fasting glucose concentrations stayed within normal range throughout the study. Treatment with a long-acting GLP1 receptor agonist revealed substantial reduction of food intake and body weight within four weeks, with increased drug sensitivity relative to observations in other DIO animal models. Extensive adipose tissue inflammation and adipocyte necrosis was observed in visceral, but not subcutaneous, adipose tissue of DIO-GM.ConclusionsThe Munich DIO-GM model resembles hallmarks of the human metabolic syndrome with extensive adipose tissue inflammation and adipocyte necrosis reported for the first time. DIO-GM may be used for evaluating novel treatments of obesity and associated comorbidities. They may help to identify triggers and mechanisms of fat tissue inflammation and mechanisms preventing complete metabolic decompensation despite morbid obesity.

Dataset Information

Effects of colchicine on lipolysis and adipose tissue inflammation in adults with obesity and metabolic syndrome.

Objective

Methods

Results

Conclusions

Publications

Effects of colchicine on lipolysis and adipose tissue inflammation in adults with obesity and metabolic syndrome.

Similar Datasets

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