scholarly journals Transgenic overexpression of hexose-6-phosphate dehydrogenase in adipose tissue causes local glucocorticoid amplification and lipolysis in male mice

2014 ◽  
Vol 306 (5) ◽  
pp. E543-E551 ◽  
Author(s):  
Ying Wang ◽  
Limei Liu ◽  
Hanze Du ◽  
Yoshiko Nagaoka ◽  
Winnie Fan ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Visceral Obesity ◽  
Abdominal Fat ◽  
Fatty Acid Binding ◽  
Metabolic Phenotypes ◽  
Lipolytic Action ◽  
Glucocorticoid Production

The prereceptor activation of glucocorticoid production in adipose tissue by NADPH-dependent 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has emerged as a potential mechanism in the pathogenesis of visceral obesity and metabolic syndrome. Hexose-6-phosphate dehydrogenase (H6PDH) is an endoplasmic reticulum lumen-resident enzyme that generates cofactor NADPH and thus mediates 11β-HSD1 activity. To determine the role of adipose H6PDH in the prereceptor modulation of 11β-HSD1 and metabolic phenotypes, we generated a transgenic (Tg) mouse model overexpressing H6PDH under the control of the enhancer-promoter region of the adipocyte fatty acid-binding protein (aP2) gene (aP2/H6PDH Tg mice). Transgenic aP2/H6PDH mice exhibited relatively high expression of H6PDH and elevated corticosterone production with induction of 11β-HSD1 activity in adipose tissue. This increase in corticosterone production in aP2-H6PDH Tg mice resulted in mild abdominal fat accumulation with induction of C/EBP mRNA expression and slight weight gain. Transgenic aP2/H6PDH mice also exhibited fasting hyperglycemia and glucose intolerance with insulin resistance. In addition, the aP2/H6PDH Tg mice have elevated circulating free fatty acid levels with a concomitant increased adipose lipolytic action associated with elevated HSL mRNA and Ser660 HSL phosphorylation within abdominal fat. These results suggest that increased H6PDH expression specifically in adipose tissue is sufficient to cause intra-adipose glucocorticoid production and adverse metabolic phenotypes. These findings suggest that the aP2/H6PDH Tg mice may provide a favorable model for studying the potential impact of H6PDH in the pathogenesis of human metabolic syndrome.

Presence of fatty-acid-binding protein 4 expression in human epicardial adipose tissue in metabolic syndrome

2008 ◽  
Vol 17 (6) ◽  
pp. 392-398 ◽  
Author(s):  
Burcak Vural ◽  
Fatmahan Atalar ◽  
Cavlan Ciftci ◽  
Ayse Demirkan ◽  
Belgin Susleyici-Duman ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Epicardial Adipose Tissue ◽  
Binding Protein ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

P267 LIVER CARCINOGENESIS RELATED TO METABOLIC SYNDROME: ROLE OF FATTY ACID-BINDING PROTEIN 4

2014 ◽  
Vol 60 (1) ◽  
pp. S154
Author(s):  
A. Sannier ◽  
S. Laouirem ◽  
M. Mebarki ◽  
M. Albuquerque ◽  
P. Bedossa ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Liver Carcinogenesis ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

scholarly journals Adipocyte Fatty Acid-Binding Protein, Cardiovascular Diseases and Mortality

2021 ◽  
Vol 12 ◽  
Author(s):  
Chi-Ho Lee ◽  
David T. W. Lui ◽  
Karen S. L. Lam
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Visceral Fat ◽  
Fatty Acid Binding Protein ◽  
Inflammatory Responses ◽  
Binding Protein ◽  
Fatty Acid Binding ◽  
Fat Depots ◽  
Acid Binding Protein

It has been increasingly recognized that inflammation plays an important role in the pathogenesis of cardiovascular disease (CVD). In obesity, adipose tissue inflammation, especially in the visceral fat depots, contributes to systemic inflammation and promotes the development of atherosclerosis. Adipocyte fatty acid-binding protein (AFABP), a lipid chaperone abundantly secreted from the adipocytes and macrophages, is one of the key players mediating this adipose-vascular cross-talk, in part via its interaction with c-Jun NH2-terminal kinase (JNK) and activator protein-1 (AP-1) to form a positive feedback loop, and perpetuate inflammatory responses. In mice, selective JNK inactivation in the adipose tissue significantly reduced the expression of AFABP in their adipose tissue, as well as circulating AFABP levels. Importantly, fat transplant experiments showed that adipose-specific JNK inactivation in the visceral fat was sufficient to protect mice with apoE deficiency from atherosclerosis, with the beneficial effects attenuated by the continuous infusion of recombinant AFABP, supporting the role of AFABP as the link between visceral fat inflammation and atherosclerosis. In humans, raised circulating AFABP levels are associated with incident metabolic syndrome, type 2 diabetes and CVD, as well as non-alcoholic steatohepatitis, diabetic nephropathy and adverse renal outcomes, all being conditions closely related to inflammation and enhanced CV mortality. Collectively, these clinical data have provided support to AFABP as an important adipokine linking obesity, inflammation and CVD. This review will discuss recent findings on the role of AFABP in CVD and mortality, the possible underlying mechanisms, and pharmacological inhibition of AFABP as a potential strategy to combat CVD.

scholarly journals Adipokines and Metabolic Regulators in Human and Experimental Pulmonary Arterial Hypertension

2021 ◽  
Vol 22 (3) ◽  
pp. 1435
Author(s):  
Aimilia Papathanasiou ◽  
Fotios Spyropoulos ◽  
Zoe Michael ◽  
Kyoung Joung ◽  
Despina Briana ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Tricarboxylic Acid Cycle ◽  
Fibroblast Growth Factor 21 ◽  
Mrna Levels ◽  
Rodent Models ◽  
Fatty Acid Binding ◽  
Metabolic Regulators ◽  
Circulating Levels

Pulmonary hypertension (PH) is associated with meta-inflammation related to obesity but the role of adipose tissue in PH pathogenesis is unknown. We hypothesized that adipose tissue-derived metabolic regulators are altered in human and experimental PH. We measured circulating levels of fatty acid binding protein 4 (FABP-4), fibroblast growth factor -21 (FGF-21), adiponectin, and the mRNA levels of FABP-4, FGF-21, and peroxisome proliferator-activated receptor γ (PPARγ) in lung tissue of patients with idiopathic PH and healthy controls. We also evaluated lung and adipose tissue expression of these mediators in the three most commonly used experimental rodent models of pulmonary hypertension. Circulating levels of FABP-4, FGF-21, and adiponectin were significantly elevated in PH patients compared to controls and the mRNA levels of these regulators and PPARγ were also significantly increased in human PH lungs and in the lungs of rats with experimental PH compared to controls. These findings were coupled with increased levels of adipose tissue mRNA of genes related to glucose uptake, glycolysis, tricarboxylic acid cycle, and fatty acid oxidation in experimental PH. Our results support that metabolic alterations in human PH are recapitulated in rodent models of the disease and suggest that adipose tissue may contribute to PH pathogenesis.

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