Urocortin Neuropeptide Levels Are Impaired in the PBMCs of Overweight Children.

Sina Kavalakatt,Dhanya Madhu,Heikki A Koistinen,Sriraman Devarajan,Hessa Al-Kandari,Nada Alam-Eldin,Jaakko Tuomilehto,Maha Hammad,Shihab Kochumon,Samia Warsame,Maria Almahdi,Abdelkrim Khadir,Fahd Al-Mulla,Rasheed Ahmad,Ali Tiss,Jehad Abubaker

doi:10.3390/nu14030429

Abstract

The corticotropin-releasing hormone (CRH) and urocortins (UCNs) have been implicated in energy homeostasis and the cellular stress response. However, the expression of these neuropeptides in children remains unclear. Therefore, we determined the impact of obesity on their expression in 40 children who were normal weight, overweight, and had obesity. Peripheral blood mononuclear cells (PBMCs) and plasma were used to assess the expression of neuropeptides. THP1 cells were treated with 25 mM glucose and 200 µM palmitate, and gene expression was measured by real-time polymerase chain reaction (RT-PCR). Transcript levels of neuropeptides were decreased in PBMCs from children with increased body mass index as indicated by a significant decrease in UCN1, UCN3, and CRH mRNA in overweight and obese children. UCN3 mRNA expression was strongly correlated with UCN1, UCN2, and CRH. Exposure of THP1 cells to palmitate or a combination of high glucose and palmitate for 24 h increased CRH, UCN2, and UCN3 mRNA expression with concomitant increased levels of inflammatory and endoplasmic reticulum stress markers, suggesting a crosstalk between these neuropeptides and the cellular stress response. The differential impairment of the transcript levels of CRH and UCNs in PBMCs from overweight and obese children highlights their involvement in obesity-related metabolic and cellular stress.

Highlights

Profound changes in lifestyle such as increased food intake and reduced physical exercise have led to alarming increases in childhood obesity, raising public health concern worldwide [1]
The study population consisted of 40 children (n = 8, 10, and 22 representing normal weight, overweight, and obesity, respectively) with a mean age of 12 years
Despite not being statistically significant, glucose levels were higher in this group

Summary

Introduction

Profound changes in lifestyle such as increased food intake and reduced physical exercise have led to alarming increases in childhood obesity, raising public health concern worldwide [1]. Obesity is involved in various metabolic impairments, including insulin resistance, dyslipidemia, and hormonal imbalances, which might impact children’s growth and induce long-lasting health consequences [1,2]. Imbalance in hormonal regulation and energy homeostasis resulting from obesity induces insulin resistance and low-grade chronic inflammation. Play an important role in the regulation of energy balance and food intake as well as behavioral and endocrine responses in mammals [4,5]. They are concomitantly expressed in the brain and peripheral organs, such as the heart, pancreas, skeletal muscle, and adipose tissue [6,7,8] suggest multiple sites of interaction of central neurochemistry circuitry

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Conclusion