Serum fatty acid-binding protein 4 (FABP4) concentration is associated with insulin resistance in peripheral tissues, A clinical study

Nakamura, Ryô; Okura, Tomohiro; Fujioka, Yohei; Sumi, Keisuke; Matsuzawa, Kazuhiko; Izawa, Shoichiro; Ueta, Etsuko; Kato, Masahiko; Taniguchi, Shin‐ichi; Yamamoto, Keiji

doi:10.1371/journal.pone.0179737

Cited by 57 publications

(49 citation statements)

References 38 publications

(50 reference statements)

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“…Increases in basal FABP-4 levels have been reported in obesity and insulin resistant states [4]. We found that clinically relevant hyperinsulinemia significantly suppressed levels of FABP-4 by approximately 18%.…”

Section: Statement Of Author's Contributionssupporting

confidence: 64%

“…Check for updates chemokines [1][2][3][4][5]. These chemokines are reported to be altered in insulin resistance and have even been proposed to mediate of some of the features of insulin resistance [2][3][4][5].…”

Section: Research Articlementioning

confidence: 99%

“…These chemokines are reported to be altered in insulin resistance and have even been proposed to mediate of some of the features of insulin resistance [2][3][4][5]. However, little is known about the regulation and function of these chemokines.…”

Section: Research Articlementioning

confidence: 99%

“…Our findings confirm these results and extend them to non-obese insulin sensitive subjects as well. FABP-4 has been proposed to play a role in facilitating fatty acid and glucose-dependent insulin secretion [4,7]. It is possible that the ability of insulin to lower FABP-4 may be part of a feedback loop to prevent hyperinsulinemia [4,7].…”

Section: Statement Of Author's Contributionsmentioning

confidence: 99%

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Insulin Regulates Circulating Omentin, Fatty Acid Binding Protein-4 and Chemerin, but not Irisin in Man

K¹,

A²,

Robert³

et al. 2018

Int J Diabetes Clin Res

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Omentin, fatty acid binding protein-4 (FABP-4), chemerin and irisin are chemokines whose circulating levels are altered in insulin resistant states. However, there is limited insight into function of these chemokines as well as the potential role of insulin in the modulation of these chemokines. We tested the hypothesis that insulin alters these chemokines by measuring changes in their circulating levels in response to elevated insulin in a group of healthy non-obese subjects. Nine (4 males and 5 females) healthy non-obese (BMI 22.0 ± 1.8 kg/m 2 ) volunteers (27 ± 4 years of age) were enrolled in an IRB-approved clinical trial. Following an overnight fast, all subjects underwent a hyperinsulinemic euglycemic clamp procedure at two physiologically relevant doses of insulin administered in sequence. Subjects received 10 mU/m 2 /min of insulin for 180 minutes during the low dose period (LD), followed by the high dose period (HD) at 40 mU/m 2 /min of insulin for an additional 180 minutes. Subjects underwent serial sampling for insulin, omentin, FABP-4, chemerin and irisin at baseline and steady-state of each period of the clamp. Significant (p < 0.01) decreases were observed in omentin and FABP-4 in response to hyperinsulinemia. Chemerin and irisin were measured in 6 subjects. Significant (p < 0.01) decreases were observed in chemerin in response to hyperinsulinemia. In contrast, irisin did not change in response to exogenous insulin. Our results show that hyperinsulinemia suppresses omentin, FABP-4 and chemerin, but not irisin in healthy non-obese humans, suggesting a potential role for insulin in regulating omentin, FABP-4 and chemerin in man. ReSeARCH ARtiCleCheck for updates chemokines [1][2][3][4][5]. These chemokines are reported to be altered in insulin resistance and have even been proposed to mediate of some of the features of insulin resistance [2][3][4][5]. However, little is known about the regulation and function of these chemokines. Endogenous hyperinsulinemia is a hallmark of the insulin resistant state. Therefore, it is reasonable to invoke a potential role for this compensatory hyperinsulinemia in the regulation of these metabolically relevant chemokines. In particular, understanding the effect of elevated insulin levels in the range observed in insulin resistance in such regulation could be especially informative. We hypothesized that insulin does have a role in altering these chemokines. We tested our hypothesis by measuring changes in circulating levels of these chemokines in a group of non-obese healthy volunteers in response to elevated insulin levels in the setting of a hyperinsulinemic euglycemic clamp procedure. Our results show that hyperinsulinemia suppresses omentin, FABP-4 and chemerin, but not irisin in healthy humans, suggesting a potential role for insulin in regulating omentin, FABP-4 and chemerin. MethodsThe current study was conducted under a protocol that was approved by an Institutional Review Board. After providing written informed consent, and following successful scree...

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Section: Statement Of Author's Contributionssupporting

confidence: 64%

Section: Research Articlementioning

confidence: 99%

Section: Research Articlementioning

confidence: 99%

Section: Statement Of Author's Contributionsmentioning

confidence: 99%

See 2 more Smart Citations

Insulin Regulates Circulating Omentin, Fatty Acid Binding Protein-4 and Chemerin, but not Irisin in Man

K¹,

A²,

Robert³

et al. 2018

Int J Diabetes Clin Res

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“…Moreover, a direct insulinotropic action of FABP4, a cytosolic lipid chaperone expressed and secreted by white and brown adipocytes may act directly on pancreatic beta cells as demonstrated in previous studies showing that recombinant FABP4 administration enhanced glucose-stimulated insulin secretion in vitro and in vivo [41,42]. In a small type 2 diabetes cohort, increased serum FABP4 was correlated to enhanced insulin release [43]. Taking these findings together, lowered circulating incretins may have provoked impaired glucose tolerance with no apparent change in beta cell function to release insulin in vivo-compensated by stimulation of glucose-stimulated insulin secretion by higher circulating FABP4 and NEFA-in aTCF7L2KO mice.…”

Section: Discussionmentioning

confidence: 78%

Reduced expression of TCF7L2 in adipocyte impairs glucose tolerance associated with decreased insulin secretion, incretins levels and lipid metabolism dysregulation in male mice

Nguyen-Tu

Martínez-Sánchez

Leclerc

et al. 2020

Preprint

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Transcription factor 7-like 2 (TCF7L2) is a downstream effector of the Wnt/beta-catenin signalling pathway and its expression is critical for adipocyte development. The precise role of TCF7L2 in glucose and lipid metabolism in adult adipocytes remains to be defined. Here, we aim to investigate how changes in TCF7L2 expression in mature adipocytes affect glucose homeostasis. Tcf7l2 was selectively ablated from mature adipocytes in C57BL/6J mice using an adiponectin promoter-driven Cre recombinase to recombine alleles floxed at exon 1 of the Tcf7l2 gene. Mice lacking Tcf7l2 in mature adipocytes displayed normal body weight. Male mice exhibited normal glucose homeostasis at eight weeks of age. Male heterozygote knockout mice (aTCF7L2het) exhibited impaired glucose tolerance (AUC increased 1.14 ± 0.04 -fold, p=0.03), as assessed by intraperitoneal glucose tolerance test, and changes in fat mass at 16 weeks (increased by 1.4 ± 0.09-fold, p=0.007). Homozygote knockout mice exhibited impaired oral glucose tolerance at 16 weeks of age (AUC increased 2.15 ± 0.15-fold, p=0.0001). Islets of Langerhans exhibited impaired glucose-stimulated insulin secretion in vitro (decreased 0.54 ± 0.13-fold aTCF7L2KO vs control, p=0.02), but no changes in in vivo glucosestimulated insulin secretion. Female mice in which one or two alleles of the Tcf7l2 gene was knocked out in adipocytes displayed no changes in glucose tolerance, insulin sensitivity or insulin secretion.Plasma levels of glucagon-like peptide-1 and gastric inhibitory polypeptide were lowered in knockout mice (decreased 0.57 ± 0.03-fold and 0.41 ± 0.12-fold, p=0.04 and p=0.002, respectively), whilst plasma free fatty acids and Fatty Acid Binding Protein 4 circulating levels were increased by 1.27 ± 0.07 and 1.78 ± 0.32-fold, respectively (p=0.05 and p=0.03). Mice with biallelic Tcf7l2 deletion exposed to high fat diet for 9 weeks exhibited impaired glucose tolerance (p=0.003 at 15 min after glucose injection) which was associated with reduced in vivo glucose-stimulated insulin secretion (decreased 0.51 ± 0.03-fold, p=0.02). Thus, our data indicate that loss of Tcf7l2 gene expression in adipocytes leads to impairments on metabolic responses which are dependent on gender, age and nutritional status. Our findings further illuminate the role of TCF7L2 in the maintenance of glucose homeostasis.

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Cell shape alteration during adipogenesis is associated with coordinated matrix cues

Moldovan

Lustig

Naftaly

et al. 2018

Journal Cellular Physiology

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Obesity has become one of the leading pathophysiologic disorders in recent years. Adipose tissue is the main tissue related to obesity and is known to play a role in various physiological complications, including type 2 diabetes. To better understand how the fat tissue develops, we used an in vitro live cell imaging system to quantify the adipogenesis by means of nondestructive digital imaging to monitor the accumulation of intracellular lipid droplets (LDs), a hallmark of adipogenesis, from the macro- to the micro-scale. Analyzing the cells' shape at the single-cell level allows to quantify the cells' shape change from a fibroblast to spherical morphology, indicating the start of adipogenesis. To reveal the molecular alterations, we applied a proteomic approach using high-resolution mass spectrometry of the proliferation, confluent fibroblasts and of adipocytes. During this process, we noted the reorganization of the cells' extracellular matrix (ECM) network microenvironment from fibrillary collagen types I, III and V to collagens IV and VI, which affected the cells niche. The changes in ECM are translated for cytoskeleton remodeling according to cell fate-determining mechanisms. We quantified the cytoskeleton rearrangement of long oriented actin fibers or short cortical and disorganized fibers, associated with LDs accumulation in adipocytes. Developing in vitro models and analytical methods enable us to study differentiation into adipocytes that will advance our understanding regarding the niche conditions that affect adipogenesis. Consequently, this will enable the development of new modalities to prevent obesity and its deleterious outcomes and to develop potential treatments to battle pathophysiology-related diseases.

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Serum fatty acid-binding protein 4 (FABP4) concentration is associated with insulin resistance in peripheral tissues, A clinical study

Cited by 57 publications

References 38 publications

Insulin Regulates Circulating Omentin, Fatty Acid Binding Protein-4 and Chemerin, but not Irisin in Man

Insulin Regulates Circulating Omentin, Fatty Acid Binding Protein-4 and Chemerin, but not Irisin in Man

Reduced expression of TCF7L2 in adipocyte impairs glucose tolerance associated with decreased insulin secretion, incretins levels and lipid metabolism dysregulation in male mice

Cell shape alteration during adipogenesis is associated with coordinated matrix cues

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