Insulin resistance, systemic and regional inflammation in subcutaneous adipose tissue during weight loss in a population with obesity

Obesity is associated mainly with adipose cell enlargement in adult man (hypertrophic obesity), whereas the formation of new fat cells (hyperplastic obesity) predominates in the prepubertal age. Adipose cell size, independent of body mass index, is negatively correlated with whole body insulin sensitivity. Here, we review recent findings linking hypertrophic obesity with inflammation and a dysregulated adipose tissue, including local cellular insulin resistance with reduced IRS-1 and GLUT4 protein content. In addition, the number of preadipocytes in the abdominal subcutaneous adipose tissue capable of undergoing differentiation to adipose cells is reduced in hypertrophic obesity. This is likely to promote ectopic lipid accumulation, a well-known finding in these individuals and one that promotes insulin resistance and cardiometabolic risk. We also review recent results showing that TNFα, but not MCP-1, resistin, or IL-6, completely prevents normal adipogenesis in preadipocytes, activates Wnt signaling, and induces a macrophage-like phenotype in the preadipocytes. In fact, activated preadipocytes, rather than macrophages, may completely account for the increased release of chemokines and cytokines by the adipose tissue in obesity. Understanding the molecular mechanisms for the impaired preadipocyte differentiation in the subcutaneous adipose tissue in hypertrophic obesity is a priority since it may lead to new ways of treating obesity and its associated metabolic complications.

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Aromatase Inhibition in Healthy Men Induces Insulin Resistance, Elevated Blood Pressure, and Altered Plasma Lipids, with Limited Changes in Transcript Levels in Subcutaneous Adipose Tissue

10.1210/endo-meetings.2011.part1.p15.p1-335 ◽

2011 ◽

pp. P1-335-P1-335

Author(s):

Fraser W Gibb ◽

Kerry J McInnes ◽

Ruth Andrew ◽

Brian R Walker

Keyword(s):

Insulin Resistance ◽

Blood Pressure ◽

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Plasma Lipids ◽

Elevated Blood ◽

Aromatase Inhibition ◽

Transcript Levels ◽

Healthy Men ◽

Subcutaneous Adipose

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Subcutaneous adipose tissue insulin resistance is associated with visceral adiposity in postmenopausal women

Obesity ◽

10.1002/oby.20703 ◽

2014 ◽

Vol 22 (6) ◽

pp. 1458-1463 ◽

Cited By ~ 3

Author(s):

Beret A. Casey ◽

Wendy M. Kohrt ◽

Robert S. Schwartz ◽

Rachael E. Van Pelt

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Postmenopausal Women ◽

Subcutaneous Adipose Tissue ◽

Visceral Adiposity ◽

Subcutaneous Adipose

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Gene Expression of Adiponectin Receptors in Human Visceral and Subcutaneous Adipose Tissue Is Related to Insulin Resistance and Metabolic Parameters and Is Altered in Response to Physical Training

Diabetes Care ◽

10.2337/dc07-1257 ◽

2007 ◽

Vol 30 (12) ◽

pp. 3110-3115 ◽

Cited By ~ 65

Author(s):

M. Bluher ◽

C. J. Williams ◽

N. Kloting ◽

A. Hsi ◽

K. Ruschke ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Adipose Tissue ◽

Physical Training ◽

Subcutaneous Adipose Tissue ◽

Metabolic Parameters ◽

Adiponectin Receptors ◽

Subcutaneous Adipose

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Insulin resistance is associated with a modest increase in inflammation in subcutaneous adipose tissue of moderately obese women

Diabetologia ◽

10.1007/s00125-008-1148-z ◽

2008 ◽

Vol 51 (12) ◽

pp. 2303-2308 ◽

Cited By ~ 48

Author(s):

T. McLaughlin ◽

A. Deng ◽

O. Gonzales ◽

M. Aillaud ◽

G. Yee ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Obese Women ◽

Modest Increase ◽

Subcutaneous Adipose

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Autologous subcutaneous adipose tissue transplants improve adipose tissue metabolism and reduce insulin resistance and fatty liver in diet-induced obesity rats

Physiological Reports ◽

10.14814/phy2.12909 ◽

2016 ◽

Vol 4 (17) ◽

pp. e12909 ◽

Cited By ~ 8

Author(s):

Gonzalo Torres-Villalobos ◽

Nashla Hamdan-Pérez ◽

Andrea Díaz-Villaseñor ◽

Armando R. Tovar ◽

Ivan Torre-Villalvazo ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Fatty Liver ◽

Subcutaneous Adipose Tissue ◽

Adipose Tissue Metabolism ◽

Tissue Metabolism ◽

Diet Induced Obesity ◽

Tissue Transplants ◽

Reduce Insulin Resistance ◽

Subcutaneous Adipose

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Abdominal visceral and subcutaneous adipose tissue and associations with cardiometabolic risk in Inuit, Africans and Europeans: a cross-sectional study

BMJ Open ◽

10.1136/bmjopen-2020-038071 ◽

2020 ◽

Vol 10 (9) ◽

pp. e038071 ◽

Cited By ~ 1

Author(s):

Pernille Falberg Rønn ◽

Gregers Stig Andersen ◽

Torsten Lauritzen ◽

Dirk Lund Christensen ◽

Mette Aadahl ◽

...

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Cardiometabolic Risk ◽

Abdominal Fat ◽

Cardiometabolic Risk Factors ◽

Hepatic Insulin Resistance ◽

Cross Sectional ◽

Subcutaneous Adipose

ObjectivesAbdominal fat has been identified as a risk marker of cardiometabolic disease independent of overall adiposity. However, it is not clear whether there are ethnic disparities in this risk. We investigated the associations of visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) with cardiometabolic risk factors in three ethnic diverse populations of Inuit, Africans and Europeans.DesignCross-sectional pooled study.SettingGreenland, Kenya and Denmark.MethodsA total of 5113 participants (2933 Inuit, 1397 Africans and 783 Europeans) from three studies in Greenland, Kenya and Denmark were included. Measurements included abdominal fat distribution assessed by ultrasound, oral glucose tolerance test, hepatic insulin resistance, blood pressure and lipids. The associations were analysed using multiple linear regressions.ResultsAcross ethnic group and gender, an increase in VAT of 1 SD was associated with higher levels of hepatic insulin resistance (ranging from 14% to 28%), triglycerides (8% to 16%) and lower high-density lipoprotein cholesterol (HDL-C, −1.0 to −0.05 mmol/L) independent of body mass index. VAT showed positive associations with most of the other cardiometabolic risk factors in Inuit and Europeans, but not in Africans. In contrast, SAT was mainly associated with the outcomes in Inuit and Africans. Of notice was that higher SAT was associated with higher HDL-C in African men (0.11 mmol/L, 95% CI: 0.03 to 0.18) and with lower HDL-C in Inuit (−0.07 mmol/L, 95% CI: -0.12 to –0.02), but not in European men (−0.02 mmol/L, 95% CI: −0.09 to 0.05). Generally weaker associations were observed for women. Furthermore, the absolute levels of several of the cardiometabolic outcomes differed between the ethnic groups.ConclusionsVAT and SAT were associated with several of the cardiometabolic risk factors beyond overall adiposity. Some of these associations were specific to ethnicity, suggesting that ethnicity plays a role in the pathway from abdominal fat to selected cardiometabolic risk factors.

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Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00490.2003 ◽

2004 ◽

Vol 286 (6) ◽

pp. E941-E949 ◽

Cited By ~ 39

Author(s):

Jussi Sutinen ◽

Katja Kannisto ◽

Elena Korsheninnikova ◽

Rachel M. Fisher ◽

Ewa Ehrenborg ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Adipose Tissue ◽

Highly Active Antiretroviral Therapy ◽

Subcutaneous Adipose Tissue ◽

Binding Protein ◽

Lipid Binding ◽

Liver Fat ◽

Highly Active ◽

Subcutaneous Adipose

Highly active antiretroviral therapy (HAART) has improved the prognosis of human immunodeficiency virus (HIV)-infected patients but is associated with severe adverse events, such as lipodystrophy and insulin resistance. Rosiglitazone did not increase subcutaneous fat in patients with HAART-associated lipodystrophy (HAL) in a randomized, double-blind, placebo-controlled trial, although it attenuated insulin resistance and decreased liver fat content. The aim of this study was to examine effects of rosiglitazone on gene expression in subcutaneous adipose tissue in 30 patients with HAL. The mRNA concentrations in subcutaneous adipose tissue were measured using real-time PCR. Twenty-four-week treatment with rosiglitazone (8 mg/day) compared with placebo significantly increased the expression of adiponectin, peroxisome proliferator-activated receptor-γ (PPARγ), and PPARγ coactivator 1 and decreased IL-6 expression. Expression of other genes involved in lipogenesis, fatty acid metabolism, or glucose transport, such as acyl-CoA synthase, adipocyte lipid-binding protein, CD45, fatty acid transport protein-1 and -4, GLUT1, GLUT4, keratinocyte lipid-binding protein, lipoprotein lipase, PPARδ, and sterol regulatory element-binding protein-1c, remained unchanged. Rosiglitazone also significantly increased serum adiponectin concentration. The change in serum adiponectin concentration was inversely correlated with the change in fasting serum insulin concentration and liver fat content. In conclusion, rosiglitazone induced significant changes in gene expression in subcutaneous adipose tissue and ameliorated insulin resistance in patients with HAL. Increased expression of adiponectin might have mediated most of the favorable insulin-sensitizing effects of rosiglitazone in these patients.

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