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Loss of Uncoupling Protein 1 Expression in the Subcutaneous Adipose Tissue Predicts Childhood Obesity
Katalin Gyurina1, Mariia Yarmak1, László Sasi-Szabó1
1Institute and University Clinics of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
Insights
Human newborns possess thermogenic subcutaneous fat depots rich in uncoupling protein 1 (UCP1)-expressing adipocytes. UCP1 expression absence in children indicates early adipose tissue expansion and obesity risk.
Area of Science:
- Human physiology
- Adipose tissue biology
- Metabolic regulation
Background:
- Thermogenesis via uncoupling protein 1 (UCP1) in adipocytes is linked to energy expenditure and weight loss.
- The presence and distribution of UCP1-expressing adipocytes in early human life remain largely uncharacterized.
Purpose of the Study:
- To investigate the presence and distribution of UCP1-expressing adipocytes and thermogenic gene expression in human fetal, infant, and childhood subcutaneous adipose tissues.
- To explore the relationship between UCP1 expression, adiposity rebound, and obesity risk in children.
Main Methods:
- Immunohistochemical analysis of UCP1 distribution in subcutaneous adipose tissue.
- Quantitative assessment of thermogenic and mitochondrial gene expression.
- Correlation analysis of UCP1 expression with body mass index (BMI) z-score and adipocyte size.
Main Results:
- UCP1-expressing adipocytes are abundant in the deep subcutaneous adipose tissue of the fetal and neonatal abdominal wall, persisting through childhood.
- These adipocytes express genes associated with mitochondrial biogenesis and thermogenesis.
- Absence of UCP1 expression in children during adiposity rebound correlates with an obesity-associated gene expression signature and is negatively correlated with BMI z-score and adipocyte size.
Conclusions:
- Deep subcutaneous adipose tissue in humans is a significant depot for UCP1-expressing adipocytes from late gestation through childhood.
- UCP1 expression in adipose tissue serves as an early indicator of adipose tissue expansion and potential obesity risk in children.
Abstract:
Stimulation of thermogenesis by inducing uncoupling protein 1 (UCP1) expression in adipocytes is thought to promote weight loss by increasing energy expenditure, and it is postulated that the human newborn has thermogenic subcutaneous fat depots. However, it remains unclear whether a relevant number of UCP1-expressing (UCP1+) adipocytes exist in the early postnatal life. Here we studied the distribution of UCP1 and the expression of thermogenic genes in the subcutaneous adipose tissues of the human fetus, infant and child. We show that the deep layer of human fetal and neonatal subcutaneous fat, particularly the abdominal wall, is rich in UCP1+ adipocytes. These adipocytes develop in the late third trimester and persist throughout childhood, expressing a panel of genes linked to mitochondrial biogenesis and thermogenesis. During the early childhood adiposity rebound-a critical phase that determines obesity risk later in life-the absence of adipose tissue UCP1 expression in children with normal body mass index (BMI) correlates with an obesity-associated gene expression signature. Finally, UCP1 expression is negatively correlated with BMI z-score and adipocyte size in infants and children. Overall, our results show that the absence of UCP1 expression in adipose tissue is an early indicator of adipose tissue expansion in children.
