Diethyl Hexyl Phthalate (DEHP) is associated with insulin resistance in adipose tissue of male rat: Protective role of antioxidant vitamins (C & E)

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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Diethyl hexyl phthalate-induced changes in insulin signaling molecules and the protective role of antioxidant vitamins in gastrocnemius muscle of adult male rat

Toxicology and Applied Pharmacology ◽

10.1016/j.taap.2011.08.022 ◽

2011 ◽

Vol 257 (2) ◽

pp. 155-164 ◽

Cited By ~ 25

Author(s):

Chinnapaiyan Srinivasan ◽

Adam Ismail Khan ◽

Venkataraman Balaji ◽

Jayaraman Selvaraj ◽

Karundevi Balasubramanian

Keyword(s):

Adult Male ◽

Insulin Signaling ◽

Gastrocnemius Muscle ◽

Protective Role ◽

Signaling Molecules ◽

Antioxidant Vitamins ◽

Male Rat ◽

Adult Male Rat ◽

Induced Changes

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An Overview of Adipose Tissue ACE2 Modulation by Diet and Obesity. Potential Implications in COVID-19 Infection and Severity

International Journal of Molecular Sciences ◽

10.3390/ijms22157975 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7975

Author(s):

Saioa Gómez-Zorita ◽

Iñaki Milton-Laskibar ◽

Laura García-Arellano ◽

Marcela González ◽

María P. Portillo

Keyword(s):

Adipose Tissue ◽

Protective Role ◽

Inflammatory Factors ◽

Current Evidence ◽

Disease Outcomes ◽

Lower Activation ◽

Two Factors ◽

Obese Subjects ◽

Ace2 Gene

The present review is aimed at analysing the current evidence concerning the potential modulation of obesity and/or diet in adipose tissue ACE2. Additionally, the potential implications of these effects on COVID-19 are also addressed. The results published show that diet and obesity are two factors that effectively influence the expression of Ace2 gene in adipose tissue. However, the shifts in this gene do not always occur in the same direction, nor with the same intensity. Additionally, there is no consensus regarding the implications of increased adipose tissue ACE2 expression in health. Thus, while in some studies a protective role is attributed to ACE2 overexpression, other studies suggest otherwise. Similarly, there is much debate regarding the role played by ACE2 in COVID-19 in terms of degree of infection and disease outcomes. The greater risk of infection that may hypothetically derive from enhanced ACE2 expression is not clear since the functionality of the enzyme seems to be as important as the abundance. Thus, the greater abundance of ACE2 in adipose tissue of obese subjects may be counterbalanced by its lower activation. In addition, a protective role of ACE2 overexpression has also been suggested, associated with the increase in anti-inflammatory factors that it may produce.

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Emerging Roles for Browning of White Adipose Tissue in Prostate Cancer Malignant Behaviour

International Journal of Molecular Sciences ◽

10.3390/ijms22115560 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5560

Author(s):

Alejandro Álvarez-Artime ◽

Belén García-Soler ◽

Rosa María Sainz ◽

Juan Carlos Mayo

Keyword(s):

Prostate Cancer ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Tumor Development ◽

Cell Types ◽

Protective Role ◽

Bioactive Molecules ◽

Brown Adipose ◽

Endocrine Organs

In addition to its well-known role as an energy repository, adipose tissue is one of the largest endocrine organs in the organism due to its ability to synthesize and release different bioactive molecules. Two main types of adipose tissue have been described, namely white adipose tissue (WAT) with a classical energy storage function, and brown adipose tissue (BAT) with thermogenic activity. The prostate, an exocrine gland present in the reproductive system of most mammals, is surrounded by periprostatic adipose tissue (PPAT) that contributes to maintaining glandular homeostasis in conjunction with other cell types of the microenvironment. In pathological conditions such as the development and progression of prostate cancer, adipose tissue plays a key role through paracrine and endocrine signaling. In this context, the role of WAT has been thoroughly studied. However, the influence of BAT on prostate tumor development and progression is unclear and has received much less attention. This review tries to bring an update on the role of different factors released by WAT which may participate in the initiation, progression and metastasis, as well as to compile the available information on BAT to discuss and open a new field of knowledge about the possible protective role of BAT in prostate cancer.

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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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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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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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The role of uncoupling protein 2 in macrophages and its impact on obesity-induced adipose tissue inflammation and insulin resistance

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.014868 ◽

2020 ◽

Vol 295 (51) ◽

pp. 17535-17548

Author(s):

Xanthe A. M. H. van Dierendonck ◽

Tiphaine Sancerni ◽

Marie-Clotilde Alves-Guerra ◽

Rinke Stienstra

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Macrophage Activation ◽

Uncoupling Protein ◽

Uncoupling Protein 2 ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Obesity And Diabetes ◽

Adipose Tissue Macrophages

The development of a chronic, low-grade inflammation originating from adipose tissue in obese subjects is widely recognized to induce insulin resistance, leading to the development of type 2 diabetes. The adipose tissue microenvironment drives specific metabolic reprogramming of adipose tissue macrophages, contributing to the induction of tissue inflammation. Uncoupling protein 2 (UCP2), a mitochondrial anion carrier, is thought to separately modulate inflammatory and metabolic processes in macrophages and is up-regulated in macrophages in the context of obesity and diabetes. Here, we investigate the role of UCP2 in macrophage activation in the context of obesity-induced adipose tissue inflammation and insulin resistance. Using a myeloid-specific knockout of UCP2 (Ucp2ΔLysM), we found that UCP2 deficiency significantly increases glycolysis and oxidative respiration, both unstimulated and after inflammatory conditions. Strikingly, fatty acid loading abolished the metabolic differences between Ucp2ΔLysM macrophages and their floxed controls. Furthermore, Ucp2ΔLysM macrophages show attenuated pro-inflammatory responses toward Toll-like receptor-2 and -4 stimulation. To test the relevance of macrophage-specific Ucp2 deletion in vivo, Ucp2ΔLysM and Ucp2fl/fl mice were rendered obese and insulin resistant through high-fat feeding. Although no differences in adipose tissue inflammation or insulin resistance was found between the two genotypes, adipose tissue macrophages isolated from diet-induced obese Ucp2ΔLysM mice showed decreased TNFα secretion after ex vivo lipopolysaccharide stimulation compared with their Ucp2fl/fl littermates. Together, these results demonstrate that although UCP2 regulates both metabolism and the inflammatory response of macrophages, its activity is not crucial in shaping macrophage activation in the adipose tissue during obesity-induced insulin resistance.

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