Adipose Tissue Inflammation is Not Related to Adipose Insulin Resistance in Humans

The role of adipose tissue (AT) inflammation on AT function in humans is unclear. We tested whether AT macrophage (ATM) content, cytokine gene expression and senescent cell burden (markers of AT inflammation) predict AT insulin resistance measured as the insulin concentration that suppresses lipolysis by 50% (IC50). We studied 86 volunteers with normal weight or obesity at baseline, and a subgroup of 25 volunteers with obesity before and after weight loss. There was a strong, positive relationship between IC50 and abdominal subcutaneous and femoral fat cell size (FCS). The positive, univariate relationships between IC50 and abdominal AT inflammatory markers: CD68, CD14, CD206 ATM/100 adipocytes, senescent cells, IL-6 and TNF-α mRNA were not significant after adjustment for FCS. A 10% weight loss significantly reduced IC50, however, there was no reduction in adipose ATM content, senescent cells or cytokine gene expression. Our study suggests that commonly used markers of AT inflammation are not causally linked to AT insulin resistance, whereas FCS is a strong predictor of AT insulin resistance with respect to lipolysis.

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SUN-113 Adipocyte Morphology And Cytokine Gene Expression In Adipose Tissue From Patients Before And After Weight Loss From Bariatric Surgery

Journal of the Endocrine Society ◽

10.1210/js.2019-sun-113 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Isabel Casimiro ◽

Jeremy White ◽

Avelino De Leon ◽

Erin Hanlon ◽

Katiannah Moise ◽

...

Keyword(s):

Gene Expression ◽

Bariatric Surgery ◽

Weight Loss ◽

Adipose Tissue ◽

Cytokine Gene Expression ◽

Cytokine Gene ◽

Before And After

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Rice Bran Protein Hydrolysates Improve Insulin Resistance and Decrease Pro-inflammatory Cytokine Gene Expression in Rats Fed a High Carbohydrate-High Fat Diet

Nutrients ◽

10.3390/nu7085292 ◽

2015 ◽

Vol 7 (8) ◽

pp. 6313-6329 ◽

Cited By ~ 38

Author(s):

Kampeebhorn Boonloh ◽

Veerapol Kukongviriyapan ◽

Bunkerd Kongyingyoes ◽

Upa Kukongviriyapan ◽

Supawan Thawornchinsombut ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Rice Bran ◽

High Fat Diet ◽

Inflammatory Cytokine ◽

Cytokine Gene Expression ◽

Cytokine Gene ◽

High Fat ◽

High Carbohydrate ◽

Improve Insulin Resistance

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High-fat diets promote insulin resistance through cytokine gene expression in growing female rats

The Journal of Nutritional Biochemistry ◽

10.1016/j.jnutbio.2007.06.005 ◽

2008 ◽

Vol 19 (8) ◽

pp. 505-513 ◽

Cited By ~ 52

Author(s):

Anne M. Flanagan ◽

Jackie L. Brown ◽

Consuelo A. Santiago ◽

Pauline Y. Aad ◽

Leon J. Spicer ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Female Rats ◽

Cytokine Gene Expression ◽

Cytokine Gene ◽

High Fat ◽

High Fat Diets ◽

Fat Diets

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Regulation of cytokine gene expression by orosomucoid in neonatal swine adipose tissue

Journal of Animal Science and Biotechnology ◽

10.1186/s40104-016-0081-0 ◽

2016 ◽

Vol 7 (1) ◽

Cited By ~ 4

Author(s):

Timothy G. Ramsay ◽

Margo J. Stoll ◽

Le Ann Blomberg ◽

Thomas J. Caperna

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Cytokine Gene Expression ◽

Cytokine Gene

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Abdominal adipose tissue cytokine gene expression: relationship to obesity and metabolic risk factors

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00419.2004 ◽

2005 ◽

Vol 288 (4) ◽

pp. E741-E747 ◽

Cited By ~ 103

Author(s):

Tongjian You ◽

Rongze Yang ◽

Mary F. Lyles ◽

Dawei Gong ◽

Barbara J. Nicklas

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Fat Distribution ◽

Cytokine Gene Expression ◽

Metabolic Risk ◽

Fasting Insulin ◽

Adiponectin Gene ◽

Cytokine Gene ◽

Tnf Α ◽

Subcutaneous Adipose

Adipose tissue is a major source of inflammatory and thrombotic cytokines. This study investigated the relationship of abdominal subcutaneous adipose tissue cytokine gene expression to body composition, fat distribution, and metabolic risk during obesity. We determined body composition, abdominal fat distribution, plasma lipids, and abdominal subcutaneous fat gene expression of leptin, TNF-α, IL-6, PAI-1, and adiponectin in 20 obese, middle-aged women (BMI, 32.7 ± 0.8 kg/m2; age, 57 ± 1 yr). A subset of these women without diabetes ( n = 15) also underwent an OGTT. In all women, visceral fat volume was negatively related to leptin ( r = −0.46, P < 0.05) and tended to be negatively related to adiponectin ( r = −0.38, P = 0.09) gene expression. Among the nondiabetic women, fasting insulin ( r = 0.69, P < 0.01), 2-h insulin ( r = 0.56, P < 0.05), and HOMA index ( r = 0.59, P < 0.05) correlated positively with TNF-α gene expression; fasting insulin ( r = 0.54, P < 0.05) was positively related to, and 2-h insulin ( r = 0.49, P = 0.06) tended to be positively related to, IL-6 gene expression; and glucose area ( r = −0.56, P < 0.05) was negatively related to, and insulin area ( r = −0.49, P = 0.06) tended to be negatively related to, adiponectin gene expression. Also, adiponectin gene expression was significantly lower in women with vs. without the metabolic syndrome (adiponectin-β-actin ratio, 2.26 ± 0.46 vs. 3.31 ± 0.33, P < 0.05). We conclude that abdominal subcutaneous adipose tissue expression of inflammatory cytokines is a potential mechanism linking obesity with its metabolic comorbidities.

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Gene expression profile of CD14+ blood monocytes following lifestyle-induced weight loss in individuals with metabolic syndrome

Scientific Reports ◽

10.1038/s41598-020-74973-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Ronald Biemann ◽

Kirsten Roomp ◽

Fozia Noor ◽

Shruthi Krishnan ◽

Zhen Li ◽

...

Keyword(s):

Gene Expression ◽

Metabolic Syndrome ◽

Weight Loss ◽

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Controlled Clinical Trial ◽

Blood Monocytes ◽

Tissue Samples ◽

Before And After ◽

Subcutaneous Adipose

Abstract Lifestyle-induced weight loss is regarded as an efficient therapy to reverse metabolic syndrome (MetS) and to prevent disease progression. The objective of this study was to investigate whether lifestyle-induced weight loss modulates gene expression in circulating monocytes. We analyzed and compared gene expression in monocytes (CD14+ cells) and subcutaneous adipose tissue biopsies by unbiased mRNA profiling. Samples were obtained before and after diet-induced weight loss in well-defined male individuals in a prospective controlled clinical trial (ICTRP Trial Number: U1111-1158-3672). The BMI declined significantly (− 12.6%) in the treatment arm (N = 39) during the 6-month weight loss intervention. This was associated with a significant reduction in hsCRP (− 45.84%) and circulating CD14+ cells (− 21.0%). Four genes were differentially expressed (DEG’s) in CD14+ cells following weight loss (ZRANB1, RNF25, RB1CC1 and KMT2C). Comparative analyses of paired CD14+ monocytes and subcutaneous adipose tissue samples before and after weight loss did not identify common genes differentially regulated in both sample types. Lifestyle-induced weight loss is associated with specific changes in gene expression in circulating CD14+ monocytes, which may affect ubiquitination, histone methylation and autophagy.

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TLR4 overexpression enhances saturated fatty acid–induced inflammatory cytokine gene expression in sheep

European Journal of Inflammation ◽

10.1177/2058739218792976 ◽

2018 ◽

Vol 16 ◽

pp. 205873921879297 ◽

Cited By ~ 1

Author(s):

Xue Xu ◽

Mei-Yu Qi ◽

Shuang Liu ◽

Xu-Ting Song ◽

Jia-Nan Zhang ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Inflammatory Cytokine ◽

Saturated Fatty Acids ◽

Nuclear Factor Κb ◽

Interleukin 10 ◽

Interferon Γ ◽

Cytokine Gene Expression ◽

Cytokine Gene ◽

Factor Α

Saturated fatty acids (SFAs) can directly stimulate innate immune responses, thereby exacerbating inflammatory aspects of metabolic syndrome. Dietary SFAs act as ligands of Toll-like receptor 4 (TLR4), triggering associated signaling pathways. In this study, we investigated the role of TLR4 in palm oil SFA-associated inflammatory cytokine gene expression in monocytes/macrophages and adipose tissue using TLR4-overexpressing genetically modified sheep. SFA stimulation resulted in upregulation of interleukin-6 ( IL-6), tumor necrosis factor-α ( TNF-α), interleukin-8 ( IL-8), interferon-γ ( IFN-γ), and interleukin-10 ( IL-10), and TLR4 overexpression enhanced such SFA-induced inflammatory cytokine expression. Moreover, SFAs markedly activated MyD88-dependent signaling, including IL-1 receptor–associated kinase 4 ( IRAK4), TNF receptor–associated factor 6 ( TRAF6), and nuclear factor-κB ( NF-κB). Taken together, our results indicate that TLR4 overexpression enhances the SFA-induced inflammatory response through MyD88-dependent signaling in monocytes/macrophages and adipose tissue.

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Expression of macrophage genes within skeletal muscle correlates inversely with adiposity and insulin resistance in humans

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2017-0228 ◽

2018 ◽

Vol 43 (2) ◽

pp. 187-193 ◽

Cited By ~ 4

Author(s):

Dongmei Liu ◽

Flor Elisa Morales ◽

Heidi. B. IglayReger ◽

Mary K. Treutelaar ◽

Amy E. Rothberg ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Weight Loss ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Muscle Tissue ◽

Skeletal Muscle Tissue ◽

Obese Patients ◽

Weight Loss Intervention

Local inflammation in obese adipose tissue has been shown to contribute to insulin resistance; however, the role of macrophage infiltration within skeletal muscle is still debatable. This study aimed to evaluate the association of skeletal muscle macrophage gene expression with adiposity levels and insulin sensitivity in obese patients. Twenty-two nondiabetic obese patients and 23 healthy lean controls were included. Obese patients underwent a 3-month weight loss intervention. Macrophage gene expression in skeletal muscle (quantitative real-time polymerase chain reaction), body composition (dual-energy X-ray absorptiometry), and insulin sensitivity (homeostatic model assessment (HOMA) and oral glucose tolerance test) were compared between groups and their associations were analyzed. To validate skeletal muscle findings, we repeated the analyses with macrophage gene expression in adipose tissue. Expression levels of macrophage genes (CD68, CD11b, CD206, CD16, CD40, and CD163) were lower in skeletal muscle tissue of obese versus lean participants. Macrophage gene expression was also found to be inversely associated with adiposity, fasting insulin, and HOMA (r = −0.4 ∼ −0.6, p < 0.05), as well as positively associated with insulin sensitivity (r = 0.4 ∼ 0.8, p < 0.05). On the other hand, adipose tissue macrophage gene expression showed higher levels in obese versus lean participants, presenting a positive association with adiposity levels. Macrophage gene expression, in both skeletal and adipose tissue samples, was only minimally affected by the weight loss intervention. In contrast with the established positive relationship between adiposity and macrophage gene expression, an unexpected inverse correlation between these 2 variables was observed in skeletal muscle tissue. Additionally, muscle macrophage gene expression was inversely correlated with insulin resistance.

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Changes in adipose tissue lipolysis gene expression and insulin sensitivity after weight loss

Endocrine Connections ◽

10.1530/ec-19-0507 ◽

2020 ◽

Vol 9 (2) ◽

pp. 90-100 ◽

Cited By ~ 1

Author(s):

Monika Karczewska-Kupczewska ◽

Agnieszka Nikołajuk ◽

Radosław Majewski ◽

Remigiusz Filarski ◽

Magdalena Stefanowicz ◽

...

Keyword(s):

Gene Expression ◽

Weight Loss ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Intervention Program ◽

Dietary Intervention ◽

Normal Weight ◽

Control Group ◽

Metabolic Complications ◽

Obese Subjects

Objective Insulin resistance is a major pathophysiological link between obesity and its metabolic complications. Weight loss (WL) is an effective tool to prevent obesity-related diseases; however, the mechanisms of an improvement in insulin sensitivity (IS) after weight-reducing interventions are not completely understood. The aim of the present study was to analyze the relationships between IS and adipose tissue (AT) expression of the genes involved in the regulation of lipolysis in obese subjects after WL. Methods Fifty-two obese subjects underwent weight-reducing dietary intervention program. The control group comprised 20 normal-weight subjects, examined at baseline only. Hyperinsulinemic-euglycemic clamp and s.c. AT biopsy with subsequent gene expression analysis were performed before and after the program. Results AT expression of genes encoding lipases (PNPLA2, LIPE and MGLL) and lipid-droplet proteins enhancing (ABHD5) and inhibiting lipolysis (PLIN1 and CIDEA) were decreased in obese individuals in comparison with normal-weight individuals. The group of 38 obese participants completed dietary intervention program and clamp studies, which resulted in a significant WL and an improvement in mean IS. However, in nine subjects from this group IS did not improve in response to WL. AT expression of PNPLA2, LIPE and PLIN1 increased only in the group without IS improvement. Conclusions Excessive lipolysis may prevent an improvement in IS during WL. The change in AT PNPLA2 and LIPE expression was a negative predictor of the change in IS after WL.

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