Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus

Furuhashi, Masato; Hiramitsu, Shinya; Mita, Tomohiro; Fuseya, Takahiro; Ishimura, Shutaro; Omori, Akina; Matsumoto, Megumi; Watanabe, Yuki; Hoshina, Kyoko; Tanaka, Marenao; Moniwa, Norihito; Yoshida, Hiroyuki; Ishii, Junnichi; Miura, Tetsuji

doi:10.1194/jlr.m059469

Cited by 44 publications

(39 citation statements)

References 54 publications

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“…Several transcription factors, such as PPAR- γ , are involved in the differentiation of preadipocytes into mature adipocytes [37]. FABP4, a lipid chaperone, is expressed in adipocytes and plays an important role in the regulation of insulin sensitivity [38]. Our results showed that FABP4 increased within 4 days but inversed within 8 days.…”

Section: Discussionmentioning

confidence: 65%

Regulation of Autophagy-Related Protein and Cell Differentiation by High Mobility Group Box 1 Protein in Adipocytes

Feng

Zhang

et al. 2016

Mediators of Inflammation

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High mobility group box 1 protein (HMGB1) is a molecule related to the development of inflammation. Autophagy is vital to maintain cellular homeostasis and protect against inflammation of adipocyte injury. Our recent work focused on the relationship of HMGB1 and autophagy in 3T3-L1 cells. In vivo experimental results showed that, compared with the normal-diet group, the high-fat diet mice displayed an increase in adipocyte size in the epididymal adipose tissues. The expression levels of HMGB1 and LC3II also increased in epididymal adipose tissues in high-fat diet group compared to the normal-diet mice. The in vitro results indicated that HMGB1 protein treatment increased LC3II formation in 3T3-L1 preadipocytes in contrast to that in the control group. Furthermore, LC3II formation was inhibited through HMGB1 knockdown by siRNA. Treatment with the HMGB1 protein enhanced LC3II expression after 2 and 4 days but decreased the expression after 8 and 10 days among various differentiation stages of adipocytes. By contrast, FABP4 expression decreased on the fourth day and increased on the eighth day. Hence, the HMGB1 protein modulated autophagy-related proteins and lipid-metabolism-related genes in adipocytes and could be a new target for treatment of obesity and related metabolic diseases.

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Section: Discussionmentioning

confidence: 65%

Regulation of Autophagy-Related Protein and Cell Differentiation by High Mobility Group Box 1 Protein in Adipocytes

Feng

Zhang

et al. 2016

Mediators of Inflammation

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“…Several studies have reported the efficacy of synthetic FABP4 inhibitors against the diseases mentioned above [6, 10, 14]. Good therapeutic effects by reducing FABP4 levels were noted with the use of BMS309403 FABP4-neutralizing antibodies as well as other commonly used drugs such as sitagliptin, angiotensin II receptor blockers and omega-3 fatty acids [10, 28–30]. These promising data enable us to draw conclusions regarding the potential use of drugs reducing FABP4 levels also for protecting patients with psoriasis from cardiovascular or metabolic disorders.…”

Section: Discussionmentioning

confidence: 99%

Serum Fatty Acid‐Binding Protein 4 is Increased in Patients with Psoriasis

Baran

Świderska

Bacharewicz-Szczerbicka

et al. 2016

Lipids

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Psoriasis is associated with metabolic syndrome and cardiovascular disease. Fatty acid-binding proteins (FABP) have been recognized as predictors of these systemic disorders. The aim of this study was to assess correlations between levels of serum heart and adipocyte fatty acid-binding proteins (FABP3, FABP4) and disease severity, indicators of inflammation or metabolic disturbances, and topical treatment in psoriatic patients. Thirty-seven patients with relapse of plaque-type psoriasis and 16 healthy volunteers were recruited. Blood samples were collected before and after 14 days of therapy. Serum FABP concentrations were examined by enzyme-linked immunosorbent assay for correlation with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory or metabolic parameters, and treatment used. The median FABP4 serum levels were significantly increased (p = 0.038) in psoriatic patients, while FABP3 levels did not differ (p = 0.47) compared to the controls. No significant correlations were noted between the proteins and PASI, C-reactive protein (CRP), BMI, or levels of glucose or lipids. FABP3 significantly correlated with white blood count (p = 0.03) and aspartate aminotransferase (p = 0.04). After topical treatment, there was no significant change in serum FABP3 [11.5 (4.9–30.3) vs. 12.9 (3.5–30.3) ng/ml] (p = 0.96), whereas FABP4 was decreased [27,286 (20,344–32,257) vs. 23,034 (18,320–29,874) pg/ml] (p = 0.12), losing its basal significance. FABP4 may be a marker of psoriasis, and FABP3 may be associated with inflammation or liver disorders in psoriatic patients. FABP do not appear to be useful for determining disease severity or the effectiveness of antipsoriatic treatment.

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“…Therefore, an obese condition prior to in vivo implantation in the host of regenerative medicine may affect the characteristics of ADSC. In addition, several therapeutic drugs, including a statin [43], omega-3 fatty acid ethyl esters [44], a dipeptidyl peptidase-4 inhibitor [45], a thiazolidinedione [46], a sodium glucose cotransporter 2 inhibitor [47] and angiotensin II receptor blockers [48, 49], have been reported to modulate circulating FABP4 level. Pretreatment with such drugs in the host before regenerative medicine may influence the effects of FABP4 and FABP5 in ADSC.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome and Metabolome Analyses in Exogenous FABP4- and FABP5-Treated Adipose-Derived Stem Cells

Yamamoto¹,

Furuhashi²,

Sugaya³

et al. 2016

PLoS ONE

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Adipose-derived stem cells (ADSC), which exist near adipocytes in adipose tissue, have been used as a potential tool of regenerative medicine. Lipid chaperones, fatty acid-binding protein 4 (FABP4) and 5 (FABP5), are abundantly expressed in adipocytes. FABP4 has recently been shown to be secreted from adipocytes during lipolysis in a non-classical pathway and may act as an adipokine. Here, we investigated the role of exogenous FABP4 and FABP5 in transcriptional and metabolic regulation in ADSC. FABP4 and FABP5 were little expressed in ADSC. However, both FABP4 and FABP5 were significantly induced after adipocyte differentiation of ADSC and were secreted from the differentiated adipocytes. Analysis of microarray data, including gene ontology enrichment analysis and cascade analysis of the protein-protein interaction network using a transcription factor binding site search, demonstrated that treatment of ADSC with FABP4 or FABP5 affected several kinds of genes related to inflammatory and metabolic responses and the process of cell differentiation. Notably, myogenic factors, including myocyte enhancer factors, myogenic differentiation 1 and myogenin, were modulated by treatment of ADSC with FABP4, indicating that exogenous FABP4 treatment is partially associated with myogenesis in ADSC. Metabolome analysis showed that treatment of ADSC with FABP4 and with FABP5 similarly, but differently in extent, promoted hydrolysis and/or uptake of lipids, consequentially together with enhancement of β oxidation, inhibition of downstream of the glycolysis pathway, accumulation of amino acids, reduction of nucleic acid components and increase in the ratio of reduced and oxidized nicotinamide adenine dinucleotide phosphates (NADPH/NADP+), an indicator of reducing power, and the ratio of adenosine triphosphate and adenosine monophosphate (ATP/AMP), an indicator of the energy state, in ADSC. In conclusion, secreted FABP4 and FABP5 from adipocytes as adipokines differentially affect transcriptional and metabolic regulation in ADSC near adipocytes. The adiposity condition in the host of regenerative medicine may affect characteristics of ADSC by exposure of the balance of FABP4 and FABP5.

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Reduction of serum FABP4 level by sitagliptin, a DPP-4 inhibitor, in patients with type 2 diabetes mellitus

Cited by 44 publications

References 54 publications

Regulation of Autophagy-Related Protein and Cell Differentiation by High Mobility Group Box 1 Protein in Adipocytes

Regulation of Autophagy-Related Protein and Cell Differentiation by High Mobility Group Box 1 Protein in Adipocytes

Serum Fatty Acid‐Binding Protein 4 is Increased in Patients with Psoriasis

Transcriptome and Metabolome Analyses in Exogenous FABP4- and FABP5-Treated Adipose-Derived Stem Cells

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