Thalidomide Controls Adipose Tissue Inflammation Associated with High- Fat Diet-Induced Obesity in Mice

Nakamitsu, Patricia Z; Compri, Cecília Melleti; Pinto, Livia de Fraia; Gotardo, Érica Martins Ferreira; Oliveira, Caroline C. de; Ribeiro, Marcelo Lima; Pedrazzoli, José; Gambero, Alessandra

doi:10.2174/1871530314666141128115225

Cited by 8 publications

(8 citation statements)

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“…In obese mice, chronic thalidomide treatment was reported to decrease MCP-1 expression and macrophages infiltration in adipose tissue41. It has been reported that high serum ICAM-1 level is associated with high mortality in cirrhotic patients42.…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of common NFκB-iNOS pathway by chronic Thalidomide treatment improves Hepatopulmonary Syndrome and Muscle Wasting in rats with Biliary Cirrhosis

Lee

et al. 2016

Sci Rep

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Thalidomide can modulate the TNFα-NFκB and iNOS pathway, which involve in the pathogenesis of hepatopulmonary syndrome (HPS) and muscle wasting in cirrhosis. In bile duct ligated-cirrhotic rats, the increased circulating CD16+ (inflammatory) monocytes and its intracellular TNFα, NFκB, monocyte chemotactic protein (MCP-1) and iNOS levels were associated with increased circulating MCP-1/soluable intercellular cell adehesion molecule-1 (sICAM-1), pulmonary TNFα/NOx, up-regulated M1 polarization, exacerbated angiogenesis and hypoxemia (increased AaPO2) in bronchoalveolar lavage (BAL) fluid and pulmonary homogenates. Meanwhile, a significant correlation was noted between circulating CD16+ monocyte/M1 (%) macrophages in BAL; M1 (%) macrophages in BAL/pulmonary iNOS mRNA expression; pulmonary iNOS mRNA expression/relative pulmonary MVD; pulmonary NOx level/AaPO2; circulating CD16+ monocyte/M1 (%) macrophages in muscle homogenates; 3-nitrotyrosine (representative of peroxynitrite) concentration/M1 (%) macrophages in muscle homogenates. The in vitro data demonstrated an iNOS-dependent inhibition of thalidomide on the TNFα-stimulated angiogenesis and myogenesis in human pulmonary artery endothelial cells (HPAECs) and C2C12 myoblasts. Significantly, the co-culture of CD16+ monocyte from different rats with HPAECs, or co-culture of supernatant of above mixed cultures with HPAECs or C2C12 myoblasts stimulated angiogenesis, migration and myogenesis. Our findings demonstrate that TNFα inhibitor thalidomide markedly diminishes the severity of experimental HPS and muscle wasting by down-regulation of common peripheral and local NFκB-iNOS pathway.

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Section: Discussionmentioning

confidence: 99%

Down-regulation of common NFκB-iNOS pathway by chronic Thalidomide treatment improves Hepatopulmonary Syndrome and Muscle Wasting in rats with Biliary Cirrhosis

Lee

et al. 2016

Sci Rep

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“…Several animal studies have shown an effect of immunomodulation on adipose inflammation. ATM content and adipose tissue expression of inflammatory cytokines was lower in mice treated with methotrexate in 1 study , and the TNF inhibitor thalidomide in a separate study . These effects were also observed in obese mice treated with an MCP‐1 inhibitor .…”

Section: Discussionmentioning

confidence: 79%

Adipose Tissue Macrophages in Rheumatoid Arthritis: Prevalence, Disease‐Related Indicators, and Associations With Cardiometabolic Risk Factors

Giles

Ferrante

Broderick

et al. 2018

Arthritis Care & Research

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Objective. Adipose tissue macrophages (ATMs) are a potent source of inflammatory cytokines, with profound effects on adipose tissue function, yet their potential role in rheumatoid arthritis (RA) pathobiology is largely unstudied. Methods. Periumbilical subcutaneous adipose tissue was obtained from 36 RA patients and 22 non-RA controls frequency matched on demographics and body mass index. Samples were stained for the macrophage marker CD68, and the average proportions of ATMs, crown-like structures (periadipocyte aggregates of 3 or more ATMs), and fibrosis were compared between groups. Results. The adjusted proportion of ATMs among all nucleated cells was 76% higher in RA than in non-RA samples (37.7 versus 21.3%, respectively; P < 0.001), and the adjusted average number of crown-like structures was more than 1.5-fold higher in the RA group than in controls (0.58 versus 0.23 crown-like structure/high-power field, respectively; P = 0.001). ATMs were significantly more abundant in early RA and in those with anti-cyclic citrullinated peptide seropositivity. Users of methotrexate, leflunomide, and tumor necrosis factor inhibitors had a significantly lower proportion of ATMs compared with nonusers. Crown-like structures were significantly higher in patients with rheumatoid factor seropositivity and in those with C-reactive protein levels ≥10 mg/liter, and significantly lower among those treated with statins. Linear ATMs were significantly associated with whole-body insulin resistance, but not with serum lipids. Conclusion. ATMs and crown-like structures were more abundant in RA patients and were associated with systemic inflammation, autoimmunity, and whole-body insulin resistance, suggesting possible contributions to the RA disease process. Lower levels of ATMs and crown-like structures associated with specific RA treatments suggest that adipose tissue inflammation may be ameliorated by immunomodulation.

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“…This report suggested that thalidomide may reduce adipose tissue growth with reduced angiogenesis and inhibited preadipocyte differentiation, similar to a VEGFR-2 blocking antibody. In a recent report [14], thalidomide administration to high-fat diet-fed mice reduced visceral fat pad mass and adipocyte size. These results appear to agree with ours, although the dose of thalidomide and the treatment duration were different.…”

Section: Discussionmentioning

confidence: 99%

“…These results appear to agree with ours, although the dose of thalidomide and the treatment duration were different. The mechanism of the reduction of the visceral fat pad mass and of the adipocyte size in thalidomide-treated high-fat diet-fed mice may result from the immunosuppressive action of thalidomide [14]. The accumulation of intramyocellular lipid triglycerides is an important aspect of the insulin resistance of skeletal muscle in obesity and type 2 diabetes mellitus [15].…”

Section: Discussionmentioning

confidence: 99%

The effect of thalidomide on visceral fat pad mass and triglyceride concentration of the skeletal muscles in rats

Kim

Choi

Kim

2018

Yeungnam Univ J Med

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BackgroundBody fats, especially both of abdominal fat pad mass and skeletal muscle fat content, are inversely related to insulin action. Therefore, methods for decreasing visceral fat mass and muscle triglyceride content may be helpful for the prevention of insulin resistance.MethodsThalidomide, used for its anti-angiogenic and anti-inflammatory properties, was administered to rats for 4 weeks. A 10% solution of thalidomide in dimethyl sulfoxide was injected daily into the peritoneal cavity as much as 100 mg/kg of body weight.ResultsThe total visceral fat pad mass in the thalidomide-treated group was 11% lower than in the control group. The size of adipocytes of the epididymal fat pad mass in the thalidomide-treated group was smaller than in the control group. The intraperitoneal thalidomide treatment increased triglyceride concentrations by 16% in the red muscle, but not in the white muscle.ConclusionThe results suggested that intraperitoneal thalidomide treatment inhibited abdominal fat accumulation, and that the free fatty acids in the blood were preferentially accumulated in the red muscle rather than in the white muscle.

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Thalidomide Controls Adipose Tissue Inflammation Associated with High- Fat Diet-Induced Obesity in Mice

Abstract: Our results suggest that drugs that can modulate the inflammatory status as well as control adipose tissue expansion could represent an interesting approach in the management of obesity, highlighting the need for further development of such compounds.

Cited by 8 publications

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Down-regulation of common NFκB-iNOS pathway by chronic Thalidomide treatment improves Hepatopulmonary Syndrome and Muscle Wasting in rats with Biliary Cirrhosis

Down-regulation of common NFκB-iNOS pathway by chronic Thalidomide treatment improves Hepatopulmonary Syndrome and Muscle Wasting in rats with Biliary Cirrhosis

Adipose Tissue Macrophages in Rheumatoid Arthritis: Prevalence, Disease‐Related Indicators, and Associations With Cardiometabolic Risk Factors

The effect of thalidomide on visceral fat pad mass and triglyceride concentration of the skeletal muscles in rats

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