Possible increase in serum FABP4 level despite adiposity reduction by canagliflozin, an SGLT2 inhibitor

Masato Furuhashi, Megumi Matsumoto, Shinya Hiramitsu, Akina Omori, Marenao Tanaka, Norihito Moniwa, Hideaki Yoshida, Junnichi Ishii, Tetsuji Miura

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is secreted from adipocytes in association with catecholamine-induced lipolysis, and elevated serum FABP4 level is associated with obesity, insulin resistance and atherosclerosis. Secreted FABP4 as a novel adipokine leads to insulin resistance via increased hepatic glucose production (HGP). Sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease blood glucose level via increased urinary glucose excretion, though HGP is enhanced. Here we investigated whether canagliflozin, an SGLT2 inhibitor, modulates serum FABP4 level. Methods Canagliflozin (100 mg/day) was administered to type 2 diabetic patients (n = 39) for 12 weeks. Serum FABP4 level was measured before and after treatment. Results At baseline, serum FABP4 level was correlated with adiposity, renal dysfunction and noradrenaline level. Treatment with canagliflozin significantly decreased adiposity and levels of fasting glucose and HbA1c but increased average serum FABP4 level by 10.3% (18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml, P = 0.008), though elevation of FABP4 level after treatment was observed in 26 (66.7%) out of 39 patients. Change in FABP4 level was positively correlated with change in levels of fasting glucose (r = 0.329, P = 0.044), HbA1c (r = 0.329, P = 0.044) and noradrenaline (r = 0.329, P = 0.041) but was not significantly correlated with change in adiposity or other variables. Conclusions Canagliflozin paradoxically increases serum FABP4 level in some diabetic patients despite amelioration of glucose metabolism and adiposity reduction, possibly via induction of catecholamine-induced lipolysis in adipocytes. Increased FABP4 level by canagliflozin may undermine the improvement of glucose metabolism and might be a possible mechanism of increased HGP by inhibition of SGLT2.

Original languageEnglish
Article numbere0154482
JournalPloS one
Volume11
Issue number4
DOIs
Publication statusPublished - 04-2016

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Sodium-Glucose Transport Proteins
Adiposity
adiposity
sodium
Glucose
glucose
Serum
Lipolysis
Adipocytes
Metabolism
Catecholamines
glycohemoglobin
Insulin Resistance
Fasting
Norepinephrine
lipolysis
catecholamines
norepinephrine
adipocytes
insulin resistance

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Furuhashi, M., Matsumoto, M., Hiramitsu, S., Omori, A., Tanaka, M., Moniwa, N., ... Miura, T. (2016). Possible increase in serum FABP4 level despite adiposity reduction by canagliflozin, an SGLT2 inhibitor. PloS one, 11(4), [e0154482]. https://doi.org/10.1371/journal.pone.0154482
Furuhashi, Masato ; Matsumoto, Megumi ; Hiramitsu, Shinya ; Omori, Akina ; Tanaka, Marenao ; Moniwa, Norihito ; Yoshida, Hideaki ; Ishii, Junnichi ; Miura, Tetsuji. / Possible increase in serum FABP4 level despite adiposity reduction by canagliflozin, an SGLT2 inhibitor. In: PloS one. 2016 ; Vol. 11, No. 4.
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title = "Possible increase in serum FABP4 level despite adiposity reduction by canagliflozin, an SGLT2 inhibitor",
abstract = "Background Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is secreted from adipocytes in association with catecholamine-induced lipolysis, and elevated serum FABP4 level is associated with obesity, insulin resistance and atherosclerosis. Secreted FABP4 as a novel adipokine leads to insulin resistance via increased hepatic glucose production (HGP). Sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease blood glucose level via increased urinary glucose excretion, though HGP is enhanced. Here we investigated whether canagliflozin, an SGLT2 inhibitor, modulates serum FABP4 level. Methods Canagliflozin (100 mg/day) was administered to type 2 diabetic patients (n = 39) for 12 weeks. Serum FABP4 level was measured before and after treatment. Results At baseline, serum FABP4 level was correlated with adiposity, renal dysfunction and noradrenaline level. Treatment with canagliflozin significantly decreased adiposity and levels of fasting glucose and HbA1c but increased average serum FABP4 level by 10.3{\%} (18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml, P = 0.008), though elevation of FABP4 level after treatment was observed in 26 (66.7{\%}) out of 39 patients. Change in FABP4 level was positively correlated with change in levels of fasting glucose (r = 0.329, P = 0.044), HbA1c (r = 0.329, P = 0.044) and noradrenaline (r = 0.329, P = 0.041) but was not significantly correlated with change in adiposity or other variables. Conclusions Canagliflozin paradoxically increases serum FABP4 level in some diabetic patients despite amelioration of glucose metabolism and adiposity reduction, possibly via induction of catecholamine-induced lipolysis in adipocytes. Increased FABP4 level by canagliflozin may undermine the improvement of glucose metabolism and might be a possible mechanism of increased HGP by inhibition of SGLT2.",
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Furuhashi, M, Matsumoto, M, Hiramitsu, S, Omori, A, Tanaka, M, Moniwa, N, Yoshida, H, Ishii, J & Miura, T 2016, 'Possible increase in serum FABP4 level despite adiposity reduction by canagliflozin, an SGLT2 inhibitor', PloS one, vol. 11, no. 4, e0154482. https://doi.org/10.1371/journal.pone.0154482

Possible increase in serum FABP4 level despite adiposity reduction by canagliflozin, an SGLT2 inhibitor. / Furuhashi, Masato; Matsumoto, Megumi; Hiramitsu, Shinya; Omori, Akina; Tanaka, Marenao; Moniwa, Norihito; Yoshida, Hideaki; Ishii, Junnichi; Miura, Tetsuji.

In: PloS one, Vol. 11, No. 4, e0154482, 04.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Possible increase in serum FABP4 level despite adiposity reduction by canagliflozin, an SGLT2 inhibitor

AU - Furuhashi, Masato

AU - Matsumoto, Megumi

AU - Hiramitsu, Shinya

AU - Omori, Akina

AU - Tanaka, Marenao

AU - Moniwa, Norihito

AU - Yoshida, Hideaki

AU - Ishii, Junnichi

AU - Miura, Tetsuji

PY - 2016/4

Y1 - 2016/4

N2 - Background Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is secreted from adipocytes in association with catecholamine-induced lipolysis, and elevated serum FABP4 level is associated with obesity, insulin resistance and atherosclerosis. Secreted FABP4 as a novel adipokine leads to insulin resistance via increased hepatic glucose production (HGP). Sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease blood glucose level via increased urinary glucose excretion, though HGP is enhanced. Here we investigated whether canagliflozin, an SGLT2 inhibitor, modulates serum FABP4 level. Methods Canagliflozin (100 mg/day) was administered to type 2 diabetic patients (n = 39) for 12 weeks. Serum FABP4 level was measured before and after treatment. Results At baseline, serum FABP4 level was correlated with adiposity, renal dysfunction and noradrenaline level. Treatment with canagliflozin significantly decreased adiposity and levels of fasting glucose and HbA1c but increased average serum FABP4 level by 10.3% (18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml, P = 0.008), though elevation of FABP4 level after treatment was observed in 26 (66.7%) out of 39 patients. Change in FABP4 level was positively correlated with change in levels of fasting glucose (r = 0.329, P = 0.044), HbA1c (r = 0.329, P = 0.044) and noradrenaline (r = 0.329, P = 0.041) but was not significantly correlated with change in adiposity or other variables. Conclusions Canagliflozin paradoxically increases serum FABP4 level in some diabetic patients despite amelioration of glucose metabolism and adiposity reduction, possibly via induction of catecholamine-induced lipolysis in adipocytes. Increased FABP4 level by canagliflozin may undermine the improvement of glucose metabolism and might be a possible mechanism of increased HGP by inhibition of SGLT2.

AB - Background Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is secreted from adipocytes in association with catecholamine-induced lipolysis, and elevated serum FABP4 level is associated with obesity, insulin resistance and atherosclerosis. Secreted FABP4 as a novel adipokine leads to insulin resistance via increased hepatic glucose production (HGP). Sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease blood glucose level via increased urinary glucose excretion, though HGP is enhanced. Here we investigated whether canagliflozin, an SGLT2 inhibitor, modulates serum FABP4 level. Methods Canagliflozin (100 mg/day) was administered to type 2 diabetic patients (n = 39) for 12 weeks. Serum FABP4 level was measured before and after treatment. Results At baseline, serum FABP4 level was correlated with adiposity, renal dysfunction and noradrenaline level. Treatment with canagliflozin significantly decreased adiposity and levels of fasting glucose and HbA1c but increased average serum FABP4 level by 10.3% (18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml, P = 0.008), though elevation of FABP4 level after treatment was observed in 26 (66.7%) out of 39 patients. Change in FABP4 level was positively correlated with change in levels of fasting glucose (r = 0.329, P = 0.044), HbA1c (r = 0.329, P = 0.044) and noradrenaline (r = 0.329, P = 0.041) but was not significantly correlated with change in adiposity or other variables. Conclusions Canagliflozin paradoxically increases serum FABP4 level in some diabetic patients despite amelioration of glucose metabolism and adiposity reduction, possibly via induction of catecholamine-induced lipolysis in adipocytes. Increased FABP4 level by canagliflozin may undermine the improvement of glucose metabolism and might be a possible mechanism of increased HGP by inhibition of SGLT2.

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Furuhashi M, Matsumoto M, Hiramitsu S, Omori A, Tanaka M, Moniwa N et al. Possible increase in serum FABP4 level despite adiposity reduction by canagliflozin, an SGLT2 inhibitor. PloS one. 2016 Apr;11(4). e0154482. https://doi.org/10.1371/journal.pone.0154482