Abstract
PurposePeople with obesity have a compromised browning capacity of adipose tissue when faced with sympathetic stimuli. This study aimed to determine whether norepinephrine treatment can enhance the induction of precursor cells from human white adipose tissue to differentiate into adipocytes that express key markers of beige adipocytes, and if there is a difference in this capacity between normal weight and overweight individuals.MethodsStromal vascular cells derived from subcutaneous white adipose tissue of normal weight and overweight groups were induced to differentiation, with or without norepinephrine, into adipocytes. Oxygen consumption rate, lipolysis, the expression of uncoupling protein 1 and other thermogenic genes were compared between different adiposity and treatment groups.ResultsPeroxisome proliferator activated receptor γ- coactivator-1 alpha (PGC-1 α) and uncoupling protein 1 gene expression increased significantly in the normal weight group, but not in the overweight group, with norepinephrine treatment. The increments of lipolysis and oxygen consumption rate were also higher in adipocytes from the normal weight group with norepinephrine treatment, as compared with those of the overweight group. PR domain containing protein 16 (PRDM 16) gene expression was higher in the normal weight group compared with that in the overweight group, while there were no significant changes found with norepinephrine treatment in either the normal weight or overweight group.ConclusionsAdipogenic precursor cells derived from overweight individuals were less prone to differentiate into beige-like adipocytes when facing sympathetic stimuli than normal weight ones, resulting in the compromised sympathetic-induced browning capacity in subcutaneous white adipose tissue in overweight individuals, which occurred before the onset of overt obesity.
Highlights
Brown adipose tissue (BAT) dissipates energy as heat via the action of uncoupling protein 1 (UCP-1), which is metabolically active in human, and greater human BAT activity is associated with lower adiposity and glycemia, suggesting regulatory links with energy metabolism
In the present study, we aimed at elucidating whether compromised adipocytebrowning plasticity occurs at an overweight stage, before the onset of overt obesity, usually the expression of beige adipocytes specific genes and protein was used to evaluate the browning capacity of adipocytes, including beige adipocytes marker protein UCP-1, thermogenic genes Peroxisome proliferator activated receptor γ (PPARγ), PPARγ coactivator-1 alpha (PGC-1α), PR domain containing protein 16 (PRDM16) and specific marker molecular of beige pre-adipocytes early B-cell factor 2 (EBf2) et al To achieve this aim, we recruited overweight individuals and determined whether norepinephrine treatment could augment the induction of primary precursor cells isolated from human subcutaneous WAT to differentiate in vitro into adipocytes that express key markers of beige adipocytes
Stromal vascular cells (SVCs) derived from 50 adipose-tissue samples were used for EBf2 gene expression analysis, and those derived from another 20 adiposetissue samples were used for primary adipocyte cultures
Summary
Brown adipose tissue (BAT) dissipates energy as heat via the action of uncoupling protein 1 (UCP-1), which is metabolically active in human, and greater human BAT (hBAT) activity is associated with lower adiposity and glycemia, suggesting regulatory links with energy metabolism. HBAT can be activated via acute, oral administration of sympathomimetic ephedrine in lean, but not obese, individuals [10]. It is not presently known whether the relationship between reduced hBAT activity and obesity is correlational or causal in nature. In the present study, we aimed at elucidating whether compromised adipocytebrowning plasticity occurs at an overweight stage, before the onset of overt obesity, usually the expression of beige adipocytes specific genes and protein was used to evaluate the browning capacity of adipocytes, including beige adipocytes marker protein UCP-1, thermogenic genes Peroxisome proliferator activated receptor γ (PPARγ), PPARγ coactivator-1 alpha (PGC-1α), PR domain containing protein 16 (PRDM16) and specific marker molecular of beige pre-adipocytes early B-cell factor 2 (EBf2) et al To achieve this aim, we recruited overweight individuals and determined whether norepinephrine treatment could augment the induction of primary precursor cells isolated from human subcutaneous WAT to differentiate in vitro into adipocytes that express key markers of beige adipocytes
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