Circulating FABP4 and FABP5 Levels Are Differently Linked to OSA Severity and Treatment

Catalá, Raquel Poquet; Cabré, Anna; Hernández-Flix, Salvador; Ferré, Raimón; Sangenís, Sandra; Plana, Núria; Texidó, Anna

doi:10.5665/sleep.3210

Cited by 13 publications

(6 citation statements)

References 31 publications

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“…The results showing distinct independent associations of increased FABP4 level with female gender, waist circumference as an index of adiposity, renal dysfunction indicated by low eGFR, and hypertriglyceridemia were in agreement with results of previous studies showing the same associations in a general population and in patients with several metabolic disorders ( 13 , 14 , 22 , 23 ), though the correlations were not strong probably due to the modulation of several concomitant drugs for diabetes mellitus, dyslipidemia and hypertension in the present study as a real-world setting. It has been shown that circulating FABP5 exists at levels of about a half or less of circulating FABP4 ( 14 , 32 – 34 , 42 , 43 ), as was confirmed in the present study. It has been shown that FABP5 concentration are related to several metabolic markers, though the correlation is not stronger than that of FABP4 ( 14 , 33 , 34 ).…”

Section: Discussionsupporting

confidence: 90%

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Independent and Distinct Associations of FABP4 and FABP5 With Metabolic Parameters in Type 2 Diabetes Mellitus

et al. 2020

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Among fatty acid-binding proteins (FABPs), secreted forms of FABP4 and FABP5, which are expressed in adipocytes and macrophages, act as bioactive molecules. We investigated concentrations of FABP4 and FABP5 in patients with type 2 diabetes mellitus. Methods: As a sub-analysis study of the Randomized Evaluation of Anagliptin vs. Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial, 256 patients (male/female: 146/110, age: 68 ± 10 years) with type 2 diabetes mellitus and dyslipidemia who were receiving statin therapy were recruited. Patients who had been treated with a thiazolidinedione were excluded. Results: Several drugs which may modulate FABP4 levels including statins, dipeptidyl peptidase-4 inhibitors and angiotensin II receptor blockers had been administered in 100, 81, and 51% of the recruited patients, respectively. The level of FABP4, but not that of FABP5, was significantly higher in females than in males. Multivariable linear regression analysis demonstrated that waist circumference (β = 0.21), estimated glomerular filtration rate (β = −0.31), triglycerides (β = 0.16), and FABP5 (β = 0.39) were independent predictors of FABP4 level after adjusting age and sex. On the other hand, FABP5 level was independently associated with levels of FABP4 (β = 0.57) and high-density lipoprotein (HDL) cholesterol (β = −0.12). Conclusions: Concentrations of FABP4 and FABP5 are independent predictors of each other in patients with type 2 diabetes mellitus. There are distinct independent associations of FABP4 with renal dysfunction, adiposity and hypertriglyceridemia and there is a distinct independent association of FABP5 with a low HDL cholesterol level in type 2 diabetic patients with dyslipidemia at high risks for cardiovascular disease who are receiving statin therapy.

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Section: Discussionsupporting

confidence: 90%

“…Taken together, the results showing that circulating levels of FABP4 and FABP5 were independent predictors of each other are reasonable. Previous studies also revealed a positive correlation between concentrations of FABP4 and FABP5 in several populations ( 32 – 34 , 42 , 43 ).…”

Section: Discussionmentioning

confidence: 62%

Independent and Distinct Associations of FABP4 and FABP5 With Metabolic Parameters in Type 2 Diabetes Mellitus

et al. 2020

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“…Similar findings had been observed in humans, where circulating AFABP concentration was associated with increasing lobular inflammation, hepatocyte ballooning and higher stages of hepatic fibrosis on liver histology ( 94 ). On the other hand, elevated serum AFABP concentration was also found in patients with severe OSA compared with those with milder disease ( 95 , 96 ), and the use of continuous positive airway pressure was shown to reduce circulating AFABP concentrations in a recent randomized controlled study ( 97 ). Moreover, circulating AFABP was associated with adverse renal outcomes including renal deaths in patients with type 2 diabetes ( 98 ), which could possibly be a result of macrophage infiltration in the glomerulus and interstitium, ectopic expression of AFABP in the glomerulus, as well as AFABP induced increased ER stress in the mesangial cells ( 99 – 101 ).…”

Section: Afabp and Other Obesity-related Conditions With Increased Cardiovascular Riskmentioning

confidence: 99%

Adipocyte Fatty Acid-Binding Protein, Cardiovascular Diseases and Mortality

2021

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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.

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“…In addition to the cytoplasm, FABP4 can also be released into the circulation. Elevated levels of FABP4 in the circulation were found in many diseases, such as bronchopulmonary dysplasia, SLE (systemic lupus erythaematosus) patients and OSA (obstructive sleep apnoea) [ 13 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Gender difference in plasma fatty-acid-binding protein 4 levels in patients with chronic obstructive pulmonary disease

Zhang

Wang

et al. 2016

Bioscience Reports

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Circulating FABP4 and FABP5 Levels Are Differently Linked to OSA Severity and Treatment

Cited by 13 publications

References 31 publications

Independent and Distinct Associations of FABP4 and FABP5 With Metabolic Parameters in Type 2 Diabetes Mellitus

Independent and Distinct Associations of FABP4 and FABP5 With Metabolic Parameters in Type 2 Diabetes Mellitus

Adipocyte Fatty Acid-Binding Protein, Cardiovascular Diseases and Mortality

Gender difference in plasma fatty-acid-binding protein 4 levels in patients with chronic obstructive pulmonary disease

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