Meteorin-Like Protein (Metrnl) in Obesity, during Weight Loss and in Adipocyte Differentiation.

Andreas Schmid,Andreas Schäffler,Thomas Karrasch

doi:10.3390/jcm10194338

Andreas Schmid, Andreas Schäffler + Show 1 more

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https://doi.org/10.3390/jcm10194338

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Abstract

Meteorin-like protein (Metrnl) is an adipo-myokine with pleiotropic effects in adipose tissue (AT). Its systemic regulation in obesity and under weight loss is unclear. Circulating Metrnl concentrations were analyzed by ELISA in severely obese patients undergoing bariatric surgery (BS) or low calorie diet (LCD). Metrnl mRNA expression was analyzed in human and murine tissues and cell lines by quantitative real-time PCR. About 312 morbidly obese individuals underwent BS (n = 181; BMI 53.4 + 6.8 kg/m2) or LCD (n = 131; BMI 43.5 + 6.7 kg/m2). Serum samples were obtained at baseline and 3, 6, and 12 months after intervention. AT specimen from subcutaneous and visceral adipose tissue were resected during BS. Serum Metrnl levels were lower in type 2 diabetic patients and negatively correlated with HbA1c. In BS and LCD patients, Metrnl concentrations significantly increased after 3 months and returned to baseline levels after 12 months. There was no gender-specific effect. Metrnl mRNA expression did not differ between visceral and subcutaneous AT in n = 130 patients. In contrast, Metrnl gene expression in mice was highest in intra-abdominal AT followed by subcutaneous, peri-renal, and brown AT. In the murine 3T3-L1 cell line, Metrnl expression was high in pre-adipocytes and mature adipocytes with a transient downregulation during adipocyte differentiation. Metrnl expression remained unaffected upon treatment with glucose, insulin, fatty acids, bile acids, and incretins. Polyunsaturated omega-3 and omega-6 fatty acids downregulated Metrnl expression. Systemic Metrnl is transiently upregulated during massive weight loss and gene expression in adipocytes is differentially regulated.

Highlights

The adipose tissue represents an endocrine and immunological organ with pleiotropic functions exerting an important role in whole body metabolism with a highly significant clinical impact [1,2]
Quantification of Baseline Meteorin-like protein (Metrnl) Serum Levels in Patients Undergoing low calorie diet (LCD) or Circulating Metrnl concentrations in morbidly obese patients were quantified by ELISA prior to weight loss induced by either LCD (n = 131; 88 females, 43 males; BMI = 43.48 ± 6.74 kg/m2)
Metrnl expression is on equal levels in visceral and subcutaneous adipose tissue and circulating Metrnl protein concentrations are not correlated with adipose tissue gene expression suggesting additional sources of Metrnl secretion that contribute to the systemic and circulating protein quantities

Summary

Introduction

The adipose tissue represents an endocrine and immunological organ with pleiotropic functions exerting an important role in whole body metabolism with a highly significant clinical impact [1,2]. Its systemic functions are mediated by a number of various secretory peptides and proteins (adipokines) that are involved in diverse physiological processes, in metabolism, inflammation, and immunity [1,3,4,5,6]. Meteorin-like protein (Metrnl; subfatin) represents a secretory protein with a molecular weight of ~30 kDa and a neurotrophic factor homologous to meteorin [10] and has a role in neuroblast migration and neuroprotection [11]. Of note, this protein is abundant in cerebrospinal fluid with its concentrations depending on blood-brain-barrier function [12].

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