The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance

Gijs H. Goossens

doi:10.1016/j.physbeh.2007.10.010

Hyperandrogenism, Insulin Resistance, and Acanthosis Nigricans (HAIR-AN) Syndrome Reflects Adipose Tissue Dysfunction (“Adiposopathy” or “Sick Fat”) in Asian Indian Girls

Dermatology ◽

10.1159/000512918 ◽

2021 ◽

pp. 1-9

Author(s):

Kritika Agrawal ◽

Rachita Mathur ◽

Naincy Purwar ◽

Sandeep Kumar Mathur ◽

Deepak Kumar Mathur

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Inflammatory Markers ◽

Tertiary Care ◽

Serum Adiponectin ◽

Primary Role ◽

Care Hospital ◽

Adipose Tissue Dysfunction ◽

Tnf Α

Background: Whether HAIR-AN syndrome and polycystic ovarian syndrome (PCOS) are distinct entities or represent a phenotypic spectrum of the same syndrome is still unclear. HAIR-AN syndrome is characterized by high insulin resistance, obesity, and hyperinsulinemia as compared to PCOS and could represent adipose tissue dysfunction as the primary pathophysiologic trigger. This study was undertaken to study the role of adipose tissue dysfunction in HAIR-AN syndrome and PCOS using adipocytokines as surrogate markers of “adiposopathy.” Materials and Methods: A cross-sectional observational study was conducted at a tertiary care hospital over a period of 1 year. Serum adiponectin, leptin, IL-6, and TNF-α levels were measured in 30 women with HAIR-AN syndrome and in 30 women with PCOS. Correlations between adipocytokines, inflammatory markers, serum testosterone, and serum insulin were determined. Data analysis was performed using the SPSS version 23.0 (IBM SPSS Statistics Inc., Chicago, IL, USA) software program. Results: Women with HAIR-AN syndrome had significantly higher hyperandrogenemia, hyperinsulinemia, and insulin resistance as compared to PCOS women. They also had high leptin levels and lower adiponectin levels (p < 0.001). However, the levels of inflammatory markers (TNF-α and IL-6) were similar in both the groups (p > 0.05). Serum adiponectin showed a negative correlation with HOMA-IR and testosterone levels, while leptin showed a positive correlation with both in HAIR-AN patients while no such correlation was found in the PCOS group. Conclusion: The significantly raised adipocytokines in HAIR-AN syndrome patients as compared to PCOS patients indicates the primary role of adipose tissue dysfunction (“adiposopathy”) in the pathogenesis of HAIR-AN syndrome while only a minor role, if any, in PCOS. Both these syndromes stand as distinct entities pathogenically with an overlapping phenotype.

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The role of obesity and adipose tissue dysfunction in gestational diabetes mellitus

Journal of Endocrinology ◽

10.1530/joe-18-0032 ◽

2018 ◽

Vol 238 (2) ◽

pp. R63-R77 ◽

Cited By ~ 13

Author(s):

Patrik Šimják ◽

Anna Cinkajzlová ◽

Kateřina Anderlová ◽

Antonín Pařízek ◽

Miloš Mráz ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Adipose Tissue ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Current Knowledge ◽

Peripheral Insulin Resistance ◽

Adipose Tissue Dysfunction ◽

History Of

Gestational diabetes mellitus is defined as diabetes diagnosed in the second or third trimester of pregnancy in patients with no history of diabetes prior to gestation. It is the most common complication of pregnancy. The underlying pathophysiology shares some common features with type 2 diabetes mellitus (T2DM) combining relatively insufficient insulin secretion with increased peripheral insulin resistance. While a certain degree of insulin resistance is the physiological characteristics of the second half of pregnancy, it is significantly more pronounced in patients with gestational diabetes. Adipose tissue dysfunction and subclinical inflammation in obesity are well-described causes of increased insulin resistance in non-pregnant subjects and are often observed in individuals with T2DM. Emerging evidence of altered adipokine expression and local inflammation in adipose tissue in patients with gestational diabetes suggests an important involvement of adipose tissue in its etiopathogenesis. This review aims to summarize current knowledge of adipose tissue dysfunction and its role in the development of gestational diabetes. We specifically focus on the significance of alterations of adipokines and immunocompetent cells number and phenotype in fat. Detailed understanding of the role of adipose tissue in gestational diabetes may provide new insights into its pathophysiology and open new possibilities of its prevention and treatment.

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Adipose tissue inflammation and metabolic dysfunction: a clinical perspective

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2013-0032 ◽

2013 ◽

Vol 15 (1) ◽

Cited By ~ 2

Author(s):

Charmaine S. Tam ◽

Leanne M. Redman

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Low Grade ◽

Metabolic Dysfunction ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Proinflammatory Mediators ◽

Low Grade Inflammation

AbstractObesity is characterized by a state of chronic low-grade inflammation due to increased immune cells, specifically infiltrated macrophages into adipose tissue, which in turn secrete a range of proinflammatory mediators. This nonselective low-grade inflammation of adipose tissue is systemic in nature and can impair insulin signaling pathways, thus, increasing the risk of developing insulin resistance and type 2 diabetes. The aim of this review is to provide an update on clinical studies examining the role of adipose tissue in the development of obesity-associated complications in humans. We will discuss adipose tissue inflammation during different scenarios of energy imbalance and metabolic dysfunction including obesity and overfeeding, weight loss by calorie restriction or bariatric surgery, and conditions of insulin resistance (diabetes, polycystic ovarian syndrome).

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Abstract 461: Role of Physical Training Intensity in Metabolic and Cardiovascular Dysfunctions in a Fructose Overload Model

Hypertension ◽

10.1161/hyp.60.suppl_1.a461 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Jacqueline F Machi ◽

Nathalia Bernardes ◽

Danielle S Dias ◽

Cristiano Mostarda ◽

Edson Moreira ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Adipose Tissue ◽

Maximum Speed ◽

Normal Range ◽

Maximal Exercise Test ◽

Baroreceptor Sensitivity ◽

Chronic Effects ◽

Male Wistar Rats

This study evaluated the chronic effects of the run and walk in the metabolic and cardiovascular parameters of a metabolic syndrome experimental model. Male Wistar rats were divided into 4 groups(n=8): Control (C),Sedentary Fructose (SF), Fructose Run (FR) and Fructose Walk (FW, n= 8). Metabolic syndrome (MS) induction was performed with D-fructose in drinking water for 18 weeks. The exercise training was initiated after the nineth week of treatment with fructose and was held for 8 weeks (60 minutes/day, 5 times / week). The FW and FR were performed on a treadmill (1 h/day; 5 days/wk for 8 wk), with ∼20% and 60% intensities respectively of the maximum speed in a maximal exercise test. Plasma glucose, triglycerides, insulin resistance, adipose tissue, blood pressure, heart rate, baroreceptor sensitivity and sympathetic and parasympathetic tone, were evaluated at the end of protocol. The results showed that run and walking decreased the adipose tissue (FR: 2.97±0.2; FW: 4.26±0.9; SF: 6.49±0.6; C: 3.23±0.2 g). The glycemia values remained within the normal range,(FR: 86.7±2.3; WF: 91.0±1.4; SF: 70.2±1.9; C: 84±2.3 mg/dl), however only the FR group decreased the triglycerides levels (FR: 133±8.8; FW: 159±10.2; SF: 220±6.3; C: 96± 4.2 mg/dl), and the insulin resistance (FR: 4.37±0.1; FW: 3.55±0.2; SF: 2.79±0.3; C: 4.86±0.3 %/min). The FR group showed a reduction in mean arterial pressure (FR: 111±4.5, FW: 125±4.1; SF: 137±2.6, C: 113±1.5 mmHg) and increased of bradycardic (FR 1.76±0.08; FW 1.31±0.10; SF 1.37±0.10; C 1.72±0.14 bpm/mmHg) and tachycardic response to BP changes (FR 4.02±0.32; FW 2.56±0.16; SF 1.97±0.15; C (and C 3.25±0.37 bpm/mmHg). Finally we observed that only the FR group showed an increase of the vagal tone (FR: 72.3±8.1, FW: 47.3±6.7; FS: 40.3±4.6, C: 60.7±6.5 bpm). In conclusion, our results suggest that training walk (FW), a practice widely recommended, is especially effective for the treatment of metabolic disorders, whereas controlled exercise (FR) seems to encompass hemodynamic and metabolic aspects. This application is easy and within reach of the majority of the population, indicating that this practice should be encouraged and may be effective in managing cardiovascular risk in MS as start therapeutic. Sources of Funding:FAPESP.

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Adipose tissue hypoxia and insulin resistance

Journal of Investigative Medicine ◽

10.1136/jim-2016-000106 ◽

2016 ◽

Vol 64 (4) ◽

pp. 830-832 ◽

Cited By ~ 14

Author(s):

Neda Rasouli

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Tissue Hypoxia ◽

Sequence Of Events ◽

Adipose Tissue Dysfunction ◽

Underlying Mechanisms ◽

Key Events

Despite the well-established association of obesity with insulin resistance and inflammation, the underlying mechanisms and sequence of events leading to inflammation and insulin resistance remain unknown. Adipose tissue hypoxia has been proposed as one of the possible key events during the process of fat expansion that leads to adipose tissue dysfunction. The focus of this paper is reviewing the evidence on adipose tissue hypoxia in obesity and its relation to insulin resistance.

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Gormony zhirovoy tkani i funktsional'nayaaktivnost' shchitovidnoy zhelezy

Obesity and metabolism ◽

10.14341/2071-8713-5081 ◽

2010 ◽

Vol 7 (4) ◽

pp. 8-11 ◽

Cited By ~ 1

Author(s):

N A Petunina ◽

N E Al'tshuler ◽

N G Rakova ◽

L V Trukhina

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Lipid Metabolism ◽

Subclinical Hypothyroidism ◽

Thyroid Dysfunction ◽

The Impact ◽

The Relationship ◽

Tissue Hormones

The review presents a recent data from the literature on the physiologic and pathophysiologic role of adipose tissue hormones (adiponectin, resistin, leptin). The article details the role of adipocytokines in atherogenesis. It also presents the results of studies depicting the relationship between subclinical hypothyroidism, lipid metabolism and insulin resistance as well as the impact of thyroid dysfunction upon the secretion of adipocytokines.

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Protocatechuic acids protects against high glucose- induced insulin resistance in human visceral adipose tissue

Problems of Endocrinology ◽

10.14341/probl201662545-46 ◽

2016 ◽

Vol 62 (5) ◽

pp. 45-46

Author(s):

Paulina Ormazabal ◽

Beatrice Scazzocchio ◽

Rosaria Varì ◽

Annunziata Iacovelli ◽

Roberta Masella

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

High Glucose ◽

Protective Role ◽

Insulin Sensitizer ◽

20 Nm ◽

Visceral Adipose

Adipocytes exposed to high glucose concentrations exhibit impaired insulin signaling. Binding of insulin to its membrane receptor activates insulin metabolic pathway leading to IRS-1 and AKT phosphorylations. The accumulation of visceral adipose tissue (VAT) correlates with insulin resistance and metabolic syndrome. Anthocyanins (ACN) are bioactive food compounds of great nutritional interest. We have shown that protocatechuic acid (PCA), a major metabolite of ACN, might exert insulin-sensitizer activities in human visceral adipose tissue. The aim of this work was to define the protective role of PCA against insulin-resistance induced by high glucose in VAT.Methodology: VAT obtained from control subject (BMI≤25) were separated in four experimental groups: i) PCA: samples treated for 24 h with 100 μM PCA, ii) GLU: VAT treated with 30 mM glucose for 24 h, iii) PCA+GLU: 1 hour incubation with 100 μM PCA before adding glucose (30 mM, 24 h), iv) CTR: vehicle. After treatment, VAT groups were (or not) acutely stimulated with insulin (20 nM, 20 min). Tyr-IRS-1 and Ser-Akt phosphorylations were assessed by Western blotting (WB) in basal or insulin stimulated tissues in all experimental groups. Samples were assessed for IRS-1, IR, Akt and GLUT4 protein content by WB. Results: No differences in protein contents between experimental groups were found. GLU tissues showed a lower increment in insulin-stimulated phosphorylation of IRS-1 and Akt compared to CTR and PCA samples. This impaired activation was completely reversed by the pretreatment with PCA.Conclusion: An in-vitro insulin-resistance condition induced by high glucose was established in biopsies of VAT. PCA restores the ability of GLU-tissues to fully respond to insulin by increasing IRS-1 and Akt phosphorylations. These results confirm the insulin-sensitizer effect of PCA on VAT previously reported by our group. An anthocyanin rich diet might help to protect against insulin-resistance in VAT.

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Osteopontin Expression in Human and Murine Obesity: Extensive Local Up-Regulation in Adipose Tissue but Minimal Systemic Alterations

Endocrinology ◽

10.1210/en.2007-1312 ◽

2007 ◽

Vol 149 (3) ◽

pp. 1350-1357 ◽

Cited By ~ 94

Author(s):

Florian W. Kiefer ◽

Maximilian Zeyda ◽

Jelena Todoric ◽

Joakim Huber ◽

René Geyeregger ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Plasma Concentrations ◽

Morbidly Obese ◽

Low Grade ◽

Obese Patients ◽

Multifunctional Protein ◽

Inflammatory Processes ◽

Low Grade Inflammation

Obesity is associated with a chronic low-grade inflammation characterized by macrophage infiltration of adipose tissue (AT) that may underlie the development of insulin resistance and type 2 diabetes. Osteopontin (OPN) is a multifunctional protein involved in various inflammatory processes, cell migration, and tissue remodeling. Because these processes occur in the AT of obese patients, we studied in detail the regulation of OPN expression in human and murine obesity. The study included 20 morbidly obese patients and 20 age- and sex-matched control subjects, as well as two models (diet-induced and genetic) of murine obesity. In high-fat diet-induced and genetically obese mice, OPN expression was drastically up-regulated in AT (40 and 80-fold, respectively) but remained largely unaltered in liver (<2-fold). Moreover, OPN plasma concentrations remained unchanged in both murine models of obesity, suggesting a particular local but not systemic importance for OPN. OPN expression was strongly elevated also in the AT of obese patients compared with lean subjects in both omental and sc AT. In addition, we detected three OPN isoforms to be expressed in human AT and, strikingly, an obesity induced alteration of the OPN isoform expression pattern. Analysis of AT cellular fractions revealed that OPN is exceptionally highly expressed in AT macrophages in humans and mice. Moreover, OPN expression in AT macrophages was strongly up-regulated by obesity. In conclusion, our data point toward a specific local role of OPN in obese AT. Therefore, OPN could be a critical regulator in obesity induced AT inflammation and insulin resistance.

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