Adipokine FABP4 integrates energy stores and counterregulatory metabolic responses

Abstract

Although counterregulatory hormones and mediators of the fight-or-flight responses are well defined at many levels, how energy stores per se are integrated into this system remains an enigmatic question. Recent years have seen the adipose tissue become a central focus for mediating intracellular signaling and communication through the release of a variety of bioactive lipids and substrates, as well as various adipokines. A critical integration node among these mediators and responses is controlled by FA binding protein 4 (FABP4), also known as adipocyte protein 2 (aP2), which is highly expressed in adipose tissue and functions as a lipid chaperone protein. Recently, it was demonstrated that FABP4 is a secreted hormone that has roles in maintaining glucose homeostasis, representing a key juncture facilitating communication between energy-storage systems and distant organs to respond to life-threatening situations. However, chronic engagement of FABP4 under conditions of immunometabolic stress, such as obesity, exacerbates a number of immunometabolic diseases, including diabetes, asthma, cancer, and atherosclerosis. In both preclinical mouse models and humans, levels of circulating FABP4 have been correlated with metabolic disease incidence, and reducing FABP4 levels or activity is associated with improved metabolic health. In this review, we will discuss the intriguing emerging biology of this protein, including potential therapeutic options for targeting circulating FABP4.

Yellow adipocytes comprise a new adipocyte sub-type present in human bone marrow

“…Surprisingly, the lipases involved in TG hydrolysis LIPE (gene name of HSL) and MGLL (gene name of MAGL) were decreased (1. 19 ± 0.80, p= 0.016 for LIPE and -2.45 ± 0.35 p =0.00024 for MGLL, see Table EV1), as well as the Fatty Acid Binding Protein 4 (FABP4), one of the most abundant proteins in adipocytes that participate in maintaining adipocyte homeostasis and regulating lipolysis and adipogenesis (Prentice et al, 2019). Finally, BM-Ad and SC-Ad exhibited distinct expression patterns of proteins involved AA metabolism and FA metabolism (Fig EV3D-E).…”

Lipid chaperones and associated diseases: a group of chaperonopathies defining a new nosological entity with implications for medical research and practice

“…1) Zimmerman and Veerkamp 1998 ; Song et al 2012 ; Tang et al 2016 ; Matsumata et al 2016 ; Chiasserini et al 2017 ; Kawahata et al 2019 FABP4 ; aP2; ALBP; AFABP; A-FABP; HEL-S-104 Fat, liver, limb, whole brain, placenta Transport of FA in intracellular compartment; Export of FA in plasma; Regulation of lipid metabolism ↑Obesity and metabolic syndrome (plasma) ↑Cardiovascular disease ↑Atherosclerosis ↑Mammary tumor risk ↓Prostate and liver cancer 132 aa (Chr. 8) Amri et al 1991 ; Makowski et al 2001 ; Boss et al 2015 ; Prentice et al 2019 ; Shen et al 1999 ; Chan et al 2010 ; Tang et al 2016 ; Hammamieh et al 2005 ; Hancke et al 2010 ; Boiteux et al 2009 ; Zhong et al 2018 FAPB5 ; EFABP; KFABP; E-FABP; PAFABP; PA-FABP Esophagus, fat, colon, skin, colon, lung, limp node, neurons, and glia Transport of FA; regulation of DHA level in the brain neuron development ↑Breast and prostate cancers ↑Psoriasis ↓Cognitive deterioration 135 aa (Chr. 3) Adamson et al 2003 ; Matsumata et al 2016 ; Pan et al 2018 FAPB6 ; ILBP; I-15P; I-BAP; ILBP3; ILLBP; I-BABP; I-BALB Small intestine Transport of FA; correct absorption and transport of bile acids ↑Colon cancer ↑Renal-cell carcinoma 128aa (Chr.…”

“…FABP4 is secreted by adipocytes in response to fasting signals (Cao et al 2013 ; Mita et al 2015 ), while in the feeding state, FABP4 secretion is suppressed by insulin (Prentice et al 2019 ). The chaperone is secreted in association with lipolysis by a non-classical secretory pathway.…”

A potential role of fatty acid binding protein 4 in the pathophysiology of autism spectrum disorder

“…Fatty acid binding protein 4 (FABP4, also known as adipocyte-FABP or aP2), a member of the FABP family ( Zimmerman and Veerkamp, 2002 ), is thought to form a complex with fatty acids (FAs) ( Gillilan et al , 2007 ) and functions as a chaperone for FAs within cells ( Furuhashi and Hotamisligil, 2008 ). FABP4 was recently identified as a novel adipokine and may play a role as an adipokine in the pathology of metabolic syndromes ( Furuhashi and Hotamisligil, 2008 ; Prentice et al , 2019 ). In our previous study, FABP4 expression was found to decrease in the scalp hair follicles of patients with schizophrenia ( Maekawa et al , 2015 ).…”