scholarly journals Changes in Adenosine 5′-Monophosphate-Activated Protein Kinase as a Mechanism of Visceral Obesity in Cushing’s Syndrome

2008 ◽  
Vol 93 (12) ◽  
pp. 4969-4973 ◽  
Author(s):  
Blerina Kola ◽  
Mirjam Christ-Crain ◽  
Francesca Lolli ◽  
Giorgio Arnaldi ◽  
Gilberta Giacchetti ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Protein Kinase ◽  
Abdominal Surgery ◽  
Visceral Adipose Tissue ◽  
Cushing’S Syndrome ◽  
Central Obesity ◽  
Cushing's Syndrome ◽  
Metabolic Effects ◽  
Ampk Activity ◽  
Visceral Adipose

Objective: Features of the metabolic syndrome such as central obesity with insulin resistance and dyslipidemia are typical signs of Cushing’s syndrome and common side effects of prolonged glucocorticoid treatment. AMP-activated protein kinase (AMPK), a key regulatory enzyme of lipid and carbohydrate metabolism as well as appetite, is involved in the development of the deleterious metabolic effects of excess glucocorticoids, but no data are available in humans. In the current study, we demonstrate the effect of high glucocorticoid levels on AMPK activity of human adipose tissue samples from patients with Cushing’s syndrome. Methods: AMPK activity and mRNA expression of genes involved in lipid metabolism were assessed in visceral adipose tissue removed at abdominal surgery of 11 patients with Cushing’s syndrome, nine sex-, age-, and weight-matched patients with adrenal incidentalomas, and in visceral adipose tissue from four patients with non-endocrine-related abdominal surgery. Results: The patients with Cushing’s syndrome exhibited a 70% lower AMPK activity in visceral adipose tissue as compared with both incidentalomas and control patients (P = 0.007 and P < 0.001, respectively). Downstream targets of AMPK fatty acid synthase and phosphoenol-pyruvate carboxykinase were up-regulated in patients with Cushing’s syndrome. AMPK activity was inversely correlated with 0900 h serum cortisol and with urinary free cortisol. Conclusions: Our data suggest that glucocorticoids inhibit AMPK activity in adipose tissue, suggesting a novel mechanism to explain the deposition of visceral adipose tissue and the consequent central obesity observed in patients with iatrogenic or endogenous Cushing’s syndrome.

scholarly journals Urinary Eicosanoid Metabolites in HIV-Infected Women with Central Obesity Switching to Raltegravir: An Analysis from the Women, Integrase, and Fat Accumulation Trial

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Todd Hulgan ◽  
M. Sean Boger ◽  
Diana H. Liao ◽  
Grace A. McComsey ◽  
Christine A. Wanke ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Hiv Infection ◽  
Visceral Adipose Tissue ◽  
Oxidant Stress ◽  
Integrase Inhibitor ◽  
Metabolic Effects ◽  
Prostaglandin E ◽  
Cross Sectional ◽  
Visceral Adipose ◽  
Adjusted Model

Chronic inflammation is a hallmark of HIV infection. Eicosanoids reflect inflammation, oxidant stress, and vascular health and vary by sex and metabolic parameters. Raltegravir (RAL) is an HIV-1 integrase inhibitor that may have limited metabolic effects. We assessed urinary F2-isoprostanes (F2-IsoPs), prostaglandin E2(PGE-M), prostacyclin (PGI-M), and thromboxane B2(TxB2) in HIV-infected women switching to RAL-containing antiretroviral therapy (ART). Thirty-seven women (RAL = 17; PI/NNRTI = 20) with a median age of 43 years and BMI 32 kg/m2completed week 24. TxB2increased in the RAL versus PI/NNRTI arm (+0.09 versus −0.02;P=0.06). Baseline PGI-M was lower in the RAL arm (P=0.005); no other between-arm cross-sectional differences were observed. In the PI/NNRTI arm, 24-week visceral adipose tissue change correlated with PGI-M (rho=0.45;P=0.04) and TxB2(rho=0.44;P=0.005) changes, with a trend seen for PGE-M (rho=0.41;P=0.07). In an adjusted model, age ≥ 50 years (N=8) was associated with increased PGE-M(P=0.04). In this randomized trial, a switch to RAL did not significantly affect urinary eicosanoids over 24 weeks. In women continuing PI/NNRTI, increased visceral adipose tissue correlated with increased PGI-M and PGE-M. Older age (≥50) was associated with increased PGE-M. Relationships between aging, adiposity, ART, and eicosanoids during HIV-infection require further study.

scholarly journals CB1 receptor mediates the effects of glucocorticoids on AMPK activity in the hypothalamus

2013 ◽  
Vol 219 (1) ◽  
pp. 79-88 ◽  
Author(s):  
Miski Scerif ◽  
Tamás Füzesi ◽  
Julia D Thomas ◽  
Blerina Kola ◽  
Ashley B Grossman ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Energy Homeostasis ◽  
Cardiac Tissue ◽  
Cannabinoid Receptor ◽  
Cushing's Syndrome ◽  
Cb1 Receptor ◽  
Metabolic Effects ◽  
Glucocorticoid Treatment ◽  
Adipose Tissues ◽  
Ampk Activity

AMP-activated protein kinase (AMPK), a regulator of cellular and systemic energy homeostasis, can be influenced by several hormones. Tissue-specific alteration of AMPK activity by glucocorticoids may explain the increase in appetite, the accumulation of lipids in adipose tissues, and the detrimental cardiac effects of Cushing's syndrome. Endocannabinoids are known to mediate the effects of various hormones and to influence AMPK activity. Cannabinoids have central orexigenic and direct peripheral metabolic effects via the cannabinoid receptor type 1 (CB1). In our preliminary experiments, WT mice received implants of a corticosterone-containing pellet to establish a mouse model of Cushing's syndrome. Subsequently, WT andCb1(Cnr1)-knockout (CB1-KO) littermates were treated with corticosterone and AMPK activity in the hypothalamus, various adipose tissues, liver and cardiac tissue was measured. Corticosterone-treated CB1-KO mice showed a lack of weight gain and of increase in hypothalamic and hepatic AMPK activity. In adipose tissues, baseline AMPK activity was higher in CB1-KO mice, but a glucocorticoid-induced drop was observed, similar to that observed in WT mice. Cardiac AMPK levels were reduced in CB1-KO mice, but while WT mice showed significantly reduced AMPK activity following glucocorticoid treatment, CB1-KO mice showed a paradoxical increase. Our findings indicate the importance of the CB1 receptor in the central orexigenic effect of glucocorticoid-induced activation of hypothalamic AMPK activity. In the periphery adipose tissues, changes may occur independently of the CB1 receptor, but the receptor appears to alter the responsiveness of the liver and myocardial tissues to glucocorticoids. In conclusion, our data suggest that an intact cannabinoid pathway is required for the full metabolic effects of chronic glucocorticoid excess.

scholarly journals Visceral adipose tissue activated macrophage content and inflammatory adipokine secretion is higher in pre-eclampsia than in healthy pregnancys

2017 ◽  
Vol 131 (13) ◽  
pp. 1529-1540 ◽  
Author(s):  
Shahzya S. Huda ◽  
Fiona Jordan ◽  
Jack Bray ◽  
Gillian Love ◽  
Reba Payne ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mrna Expression ◽  
Visceral Adipose Tissue ◽  
Clinical Syndrome ◽  
Metabolic Effects ◽  
Tissue Cell ◽  
Tissue Macrophage ◽  
Adipose Tissue Cell ◽  
Cell Densities ◽  
Visceral Adipose

Obesity increases pre-eclampsia (PE) risk. Adipose tissue inflammation may contribute to the clinical syndrome of PE. We compared adipose tissue macrophage infiltration and release of pro-inflammatory adipokines in PE and healthy pregnancy. Subcutaneous and visceral adipose tissue biopsies were collected from healthy (n=13) and PE (n=13) mothers. Basal and lipopolysaccharide (LPS) stimulated adipocyte TNFα, IL-6, CCL-2, and CRP release was measured. Adipose tissue cell densities of activated (cfms+) and total (CD68+) macrophages were determined. In PE only, visceral adipose tissue TNFα release was increased after LPS stimulation (57 [76] versus 81 [97] pg/ml/µg DNA, P=0.030). Basal TNFα release was negatively correlated insulin sensitivity of visceral adipocytes (r = −0.61, P=0.030) in PE. Visceral adipocyte IL-6 release was increased after LPS stimulation in PE only (566 [696] versus 852 [914] pg/ml/µg DNA, P=0.019). Visceral adipocyte CCL-2 basal (67 [61] versus 187 [219] pg/ml/µgDNA, P=0.049) and stimulated (46 [46] versus 224 [271] pg/ml/µg DNA, P=0.003) release was greater than in subcutaneous adipocytes in PE only. In PE, median TNF mRNA expression in visceral adipose tissue was higher than controls (1.94 [1.13–4.14] versus 0.8 [0.00–1.27] TNF/PPIA ratio, P=0.006). In visceral adipose tissue, CSF1R (a marker of activated macrophages) mRNA expression (24.8[11.0] versus 51.0[29.9] CSF1R/PPIA ratio, P=0.011) and activated (cfms+) macrophage count (6.7[2.6] versus 15.2[8.8] % cfms+/adipocyte, P=0.031) were higher in PE than in controls. In conclusion, our study demonstrates dysregulation of inflammatory pathways predominantly in visceral adipose tissue in PE. Inflammation of visceral adipose tissue may mediate many of the adverse metabolic effects associated with PE.

scholarly journals Ibuprofen increases the serum Omentin levels in rats after abdominal surgery

2020 ◽  
Vol 66 (5) ◽  
pp. 596-599
Author(s):  
Mustafa Sit ◽  
Gulali Aktas ◽  
Bahri Ozer ◽  
Oguz Catal
Keyword(s):  
Adipose Tissue ◽  
Abdominal Surgery ◽  
Visceral Adipose Tissue ◽  
Wistar Rats ◽  
Beneficial Effects ◽  
Metabolic Outcomes ◽  
Laparotomy Group ◽  
The Mean ◽  
Visceral Adipose ◽  
Circulating Levels

SUMMARY AIMS Omentin is an adipokine primarily produced by visceral adipose tissue and its reduced levels have been shown to be associate with worse metabolic outcomes. We aimed to study the effects of preoperative ibuprofen on postoperative omentin levels in rats after surgery. METHODS Forty-eight albino Wistar rats, 6 in each of 8 groups according to the surgical procedure (laparotomy, laparotomy plus ibuprofen (IBU), nephrectomy, nephrectomy plus IBU, hepatectomy, hepatectomy plus IBU, splenectomy and splenectomy plus IBU). The Omentin levels of the groups were postoperatively analyzed. RESULTS The mean omentin was significantly higher in the laparotomy plus IBU group compared to the laparotomy group (p<0.001). Mean Omentin was significantly higher in the hepatectomy plus IBU group compared to the hepatectomy group (p=0.01). Mean Omentin was significantly higher in the nephrectomy plus IBU group compared to the nephrectomy group (p=0.001). CONCLUSION We suggest that preoperative ibuprofen may enhance circulating levels of Omentin, which has beneficial effects in trauma and inflammation settings in subjects that undergo minor or major abdominal surgery.

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