Apolipoprotein M: a novel adipokine decreasing with obesity and upregulated by calorie restriction

Veronika Sramkova; Sarah Berend; Michaela Siklova; Sylvie Caspar-Bauguil; Jerome Carayol; Sophie Bonnel; Marie Marques; Pauline Decaunes; Catherine-Ines Kolditz; Ingrid Dahlman; Peter Arner; Vladimir Stich; Wim H. M. Saris; Arne Astrup; Armand Valsesia; Lenka Rossmeislova; Dominique Langin; Nathalie Viguerie

doi:10.1093/ajcn/nqy331

Apolipoprotein M: a novel adipokine decreasing with obesity and upregulated by calorie restriction

Veronika Sramkova, Sarah Berend, Michaela Siklova, Sylvie Caspar-Bauguil, Jerome Carayol, Sophie Bonnel, Marie Marques, Pauline Decaunes, Catherine-Ines Kolditz, Ingrid Dahlman, Peter Arner, Vladimir Stich, Wim H. M. Saris, Arne Astrup, Armand Valsesia, Lenka Rossmeislova, Dominique Langin, Nathalie Viguerie^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: The adipose tissue (AT) is a secretory organ producing a wide variety of factors that participate in the genesis of metabolic disorders linked to excess fat mass. Weight loss improves obesity-related disorders.

Objectives: Transcriptomic studies on human AT, and a combination of analyses of transcriptome and proteome profiling of conditioned media from adipocytes and stromal cells isolated from human AT, have led to the identification of apolipoprotein M (apoM) as a putative adipokine. We aimed to validate apoM as novel adipokine, investigate the relation of AT APOM expression with metabolic syndrome and insulin sensitivity, and study the regulation of its expression in AT and secretion during calorie restriction-induced weight loss.

Methods: We examined APOM mRNA level and secretion in AT from 485 individuals enrolled in 5 independent clinical trials, and in vitro in human multipotent adipose-derived stem cell adipocytes. APOM expression and secretion were measured during dieting.

Results: APOM was expressed in human subcutaneous and visceral AT, mainly by adipocytes. ApoM was released into circulation from AT, and plasma apoM concentrations correlate with AT APOM mRNA levels. In AT, APOM expression inversely correlated with adipocyte size, was lower in obese compared to lean individuals, and reduced in subjects with metabolic syndrome and type 2 diabetes. Regardless of fat depot, there was a positive relation between AT APOM expression and systemic insulin sensitivity, independently of fat mass and plasma HDL cholesterol. In human multipotent adipose-derived stem cell adipocytes, APOM expression was enhanced by insulin-sensitizing peroxisome proliferator-activated receptor agonists and inhibited by tumor necrosis factor a, a cytokine that causes insulin resistance. In obese individuals, calorie restriction increased AT APOM expression and secretion.

Conclusions: ApoM is a novel adipokine, the expression of which is a hallmark of healthy AT and is upregulated by calorie restriction. AT apoM deserves further investigation as a potential biomarker of risk for diabetes and cardiovascular diseases.

Original language	English
Pages (from-to)	1499-1510
Number of pages	12
Journal	American Journal of Clinical Nutrition
Volume	109
Issue number	6
DOIs	https://doi.org/10.1093/ajcn/nqy331
Publication status	Published - Jun 2019

Keywords

obesity
adipokine
adipose tissue
glucose homeostasis
insulin resistance
diet
metabolic syndrome
calorie restriction
lipocalin
BETA-HDL FORMATION
ADIPOSE-TISSUE
INSULIN SENSITIVITY
METABOLIC SYNDROME
GENE-EXPRESSION
WEIGHT-LOSS
IN-VIVO
DIET
RESISTANCE
PLASMA

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10.1093/ajcn/nqy331Licence: Free access - publisher

Cite this

Sramkova, V., Berend, S., Siklova, M., Caspar-Bauguil, S., Carayol, J., Bonnel, S., Marques, M., Decaunes, P., Kolditz, C.-I., Dahlman, I., Arner, P., Stich, V., Saris, W. H. M., Astrup, A., Valsesia, A., Rossmeislova, L., Langin, D., & Viguerie, N. (2019). Apolipoprotein M: a novel adipokine decreasing with obesity and upregulated by calorie restriction. American Journal of Clinical Nutrition, 109(6), 1499-1510. https://doi.org/10.1093/ajcn/nqy331

@article{eeaae0618d3c4b28be4915071b613dca,

title = "Apolipoprotein M: a novel adipokine decreasing with obesity and upregulated by calorie restriction",

abstract = "Background: The adipose tissue (AT) is a secretory organ producing a wide variety of factors that participate in the genesis of metabolic disorders linked to excess fat mass. Weight loss improves obesity-related disorders.Objectives: Transcriptomic studies on human AT, and a combination of analyses of transcriptome and proteome profiling of conditioned media from adipocytes and stromal cells isolated from human AT, have led to the identification of apolipoprotein M (apoM) as a putative adipokine. We aimed to validate apoM as novel adipokine, investigate the relation of AT APOM expression with metabolic syndrome and insulin sensitivity, and study the regulation of its expression in AT and secretion during calorie restriction-induced weight loss.Methods: We examined APOM mRNA level and secretion in AT from 485 individuals enrolled in 5 independent clinical trials, and in vitro in human multipotent adipose-derived stem cell adipocytes. APOM expression and secretion were measured during dieting.Results: APOM was expressed in human subcutaneous and visceral AT, mainly by adipocytes. ApoM was released into circulation from AT, and plasma apoM concentrations correlate with AT APOM mRNA levels. In AT, APOM expression inversely correlated with adipocyte size, was lower in obese compared to lean individuals, and reduced in subjects with metabolic syndrome and type 2 diabetes. Regardless of fat depot, there was a positive relation between AT APOM expression and systemic insulin sensitivity, independently of fat mass and plasma HDL cholesterol. In human multipotent adipose-derived stem cell adipocytes, APOM expression was enhanced by insulin-sensitizing peroxisome proliferator-activated receptor agonists and inhibited by tumor necrosis factor a, a cytokine that causes insulin resistance. In obese individuals, calorie restriction increased AT APOM expression and secretion.Conclusions: ApoM is a novel adipokine, the expression of which is a hallmark of healthy AT and is upregulated by calorie restriction. AT apoM deserves further investigation as a potential biomarker of risk for diabetes and cardiovascular diseases.",

keywords = "obesity, adipokine, adipose tissue, glucose homeostasis, insulin resistance, diet, metabolic syndrome, calorie restriction, lipocalin, BETA-HDL FORMATION, ADIPOSE-TISSUE, INSULIN SENSITIVITY, METABOLIC SYNDROME, GENE-EXPRESSION, WEIGHT-LOSS, IN-VIVO, DIET, RESISTANCE, PLASMA",

author = "Veronika Sramkova and Sarah Berend and Michaela Siklova and Sylvie Caspar-Bauguil and Jerome Carayol and Sophie Bonnel and Marie Marques and Pauline Decaunes and Catherine-Ines Kolditz and Ingrid Dahlman and Peter Arner and Vladimir Stich and Saris, {Wim H. M.} and Arne Astrup and Armand Valsesia and Lenka Rossmeislova and Dominique Langin and Nathalie Viguerie",

note = "Funding Information: This work was supported by Inserm, Paul Sabatier University, the Commission of the European Communities(FP6-513946 DiOGenes and FP7-201100 ADAPT) and the Innovative Medicines Initiative Joint Undertaking (EMIF, grant agreement 115372). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. DL is a member of the Institut Universitaire de France. VS and SB contributed equally to this work. Publisher Copyright: {\textcopyright} American Society for Nutrition 2019. All rights reserved.",

year = "2019",

month = jun,

doi = "10.1093/ajcn/nqy331",

language = "English",

volume = "109",

pages = "1499--1510",

journal = "American Journal of Clinical Nutrition",

issn = "0002-9165",

publisher = "Elsevier Inc.",

number = "6",

}

Sramkova, V, Berend, S, Siklova, M, Caspar-Bauguil, S, Carayol, J, Bonnel, S, Marques, M, Decaunes, P, Kolditz, C-I, Dahlman, I, Arner, P, Stich, V, Saris, WHM, Astrup, A, Valsesia, A, Rossmeislova, L, Langin, D & Viguerie, N 2019, 'Apolipoprotein M: a novel adipokine decreasing with obesity and upregulated by calorie restriction', American Journal of Clinical Nutrition, vol. 109, no. 6, pp. 1499-1510. https://doi.org/10.1093/ajcn/nqy331

TY - JOUR

T1 - Apolipoprotein M

T2 - a novel adipokine decreasing with obesity and upregulated by calorie restriction

AU - Sramkova, Veronika

AU - Berend, Sarah

AU - Siklova, Michaela

AU - Caspar-Bauguil, Sylvie

AU - Carayol, Jerome

AU - Bonnel, Sophie

AU - Marques, Marie

AU - Decaunes, Pauline

AU - Kolditz, Catherine-Ines

AU - Dahlman, Ingrid

AU - Arner, Peter

AU - Stich, Vladimir

AU - Saris, Wim H. M.

AU - Astrup, Arne

AU - Valsesia, Armand

AU - Rossmeislova, Lenka

AU - Langin, Dominique

AU - Viguerie, Nathalie

N1 - Funding Information: This work was supported by Inserm, Paul Sabatier University, the Commission of the European Communities(FP6-513946 DiOGenes and FP7-201100 ADAPT) and the Innovative Medicines Initiative Joint Undertaking (EMIF, grant agreement 115372). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. DL is a member of the Institut Universitaire de France. VS and SB contributed equally to this work. Publisher Copyright: © American Society for Nutrition 2019. All rights reserved.

PY - 2019/6

Y1 - 2019/6

N2 - Background: The adipose tissue (AT) is a secretory organ producing a wide variety of factors that participate in the genesis of metabolic disorders linked to excess fat mass. Weight loss improves obesity-related disorders.Objectives: Transcriptomic studies on human AT, and a combination of analyses of transcriptome and proteome profiling of conditioned media from adipocytes and stromal cells isolated from human AT, have led to the identification of apolipoprotein M (apoM) as a putative adipokine. We aimed to validate apoM as novel adipokine, investigate the relation of AT APOM expression with metabolic syndrome and insulin sensitivity, and study the regulation of its expression in AT and secretion during calorie restriction-induced weight loss.Methods: We examined APOM mRNA level and secretion in AT from 485 individuals enrolled in 5 independent clinical trials, and in vitro in human multipotent adipose-derived stem cell adipocytes. APOM expression and secretion were measured during dieting.Results: APOM was expressed in human subcutaneous and visceral AT, mainly by adipocytes. ApoM was released into circulation from AT, and plasma apoM concentrations correlate with AT APOM mRNA levels. In AT, APOM expression inversely correlated with adipocyte size, was lower in obese compared to lean individuals, and reduced in subjects with metabolic syndrome and type 2 diabetes. Regardless of fat depot, there was a positive relation between AT APOM expression and systemic insulin sensitivity, independently of fat mass and plasma HDL cholesterol. In human multipotent adipose-derived stem cell adipocytes, APOM expression was enhanced by insulin-sensitizing peroxisome proliferator-activated receptor agonists and inhibited by tumor necrosis factor a, a cytokine that causes insulin resistance. In obese individuals, calorie restriction increased AT APOM expression and secretion.Conclusions: ApoM is a novel adipokine, the expression of which is a hallmark of healthy AT and is upregulated by calorie restriction. AT apoM deserves further investigation as a potential biomarker of risk for diabetes and cardiovascular diseases.

AB - Background: The adipose tissue (AT) is a secretory organ producing a wide variety of factors that participate in the genesis of metabolic disorders linked to excess fat mass. Weight loss improves obesity-related disorders.Objectives: Transcriptomic studies on human AT, and a combination of analyses of transcriptome and proteome profiling of conditioned media from adipocytes and stromal cells isolated from human AT, have led to the identification of apolipoprotein M (apoM) as a putative adipokine. We aimed to validate apoM as novel adipokine, investigate the relation of AT APOM expression with metabolic syndrome and insulin sensitivity, and study the regulation of its expression in AT and secretion during calorie restriction-induced weight loss.Methods: We examined APOM mRNA level and secretion in AT from 485 individuals enrolled in 5 independent clinical trials, and in vitro in human multipotent adipose-derived stem cell adipocytes. APOM expression and secretion were measured during dieting.Results: APOM was expressed in human subcutaneous and visceral AT, mainly by adipocytes. ApoM was released into circulation from AT, and plasma apoM concentrations correlate with AT APOM mRNA levels. In AT, APOM expression inversely correlated with adipocyte size, was lower in obese compared to lean individuals, and reduced in subjects with metabolic syndrome and type 2 diabetes. Regardless of fat depot, there was a positive relation between AT APOM expression and systemic insulin sensitivity, independently of fat mass and plasma HDL cholesterol. In human multipotent adipose-derived stem cell adipocytes, APOM expression was enhanced by insulin-sensitizing peroxisome proliferator-activated receptor agonists and inhibited by tumor necrosis factor a, a cytokine that causes insulin resistance. In obese individuals, calorie restriction increased AT APOM expression and secretion.Conclusions: ApoM is a novel adipokine, the expression of which is a hallmark of healthy AT and is upregulated by calorie restriction. AT apoM deserves further investigation as a potential biomarker of risk for diabetes and cardiovascular diseases.

KW - obesity

KW - adipokine

KW - adipose tissue

KW - glucose homeostasis

KW - insulin resistance

KW - diet

KW - metabolic syndrome

KW - calorie restriction

KW - lipocalin

KW - BETA-HDL FORMATION

KW - ADIPOSE-TISSUE

KW - INSULIN SENSITIVITY

KW - METABOLIC SYNDROME

KW - GENE-EXPRESSION

KW - WEIGHT-LOSS

KW - IN-VIVO

KW - DIET

KW - RESISTANCE

KW - PLASMA

U2 - 10.1093/ajcn/nqy331

DO - 10.1093/ajcn/nqy331

M3 - Article

C2 - 30869115

SN - 0002-9165

VL - 109

SP - 1499

EP - 1510

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

IS - 6

ER -