Abstract
IntroductionBrown adipose tissue (BAT) is a potential therapeutic target to reverse obesity. The purpose of this study was to determine whether primary precursor cells isolated from human adult subcutaneous white adipose tissue (WAT) can be induced to differentiate in-vitro into adipocytes that express key markers of brown or beige adipose, and whether the expression level of such markers differs between lean and obese young adult males.MethodsAdipogenic precursor cells were isolated from lean and obese individuals from subcutaneous abdominal WAT biopsies. Cells were grown to confluence, differentiated for 2.5 weeks then harvested for measurement of gene expression and UCP1 protein.ResultsThere was no difference between groups with respect to differentiation into adipocytes, as indicated by oil red-O staining, rates of lipolysis, and expression of adipogenic genes (FABP4, PPARG). WAT genes (HOXC9, RB1) were expressed equally in the two groups. Post differentiation, the beige adipose specific genes CITED1 and CD137 were significantly increased in both groups, but classic BAT markers ZIC1 and LHX8 decreased significantly. Cell lines from both groups also equally increased post-differentiation expression of the thermogenic-responsive gene PPARGC1A (PGC-1α). UCP1 gene expression was undetectable prior to differentiation, however after differentiation both gene expression and protein content were increased in both groups and were significantly greater in cultures from lean compared with obese individuals (p<0.05).ConclusionHuman subcutaneous WAT cells can be induced to attain BAT characteristics, but this capacity is reduced in WAT cells from obese individuals.
Highlights
Brown adipose tissue (BAT) is a potential therapeutic target to reverse obesity
Using human subcutaneous white adipose tissue (WAT) precursor cells from lean and obese humans grown in brown adipose differentiation media, we aimed to determine: i) their capacity to form brown/beige adipocytes by measuring expression of representative genes and UCP-1 protein
Light microscopy (Fig 1a), and quantitation of oil red-O lipid staining (Fig 1b) indicated that cells differentiated into lipid-laden adipocytes and that there was no difference in the degree of lipid loading between cultures from lean and obese groups
Summary
Brown adipose tissue (BAT) is a potential therapeutic target to reverse obesity. The purpose of this study was to determine whether primary precursor cells isolated from human adult subcutaneous white adipose tissue (WAT) can be induced to differentiate in-vitro into adipocytes that express key markers of brown or beige adipose, and whether the expression level of such markers differs between lean and obese young adult males. Based on detailed study of cervical neck fat, humans probably contain a mix of white (WAT), brown and ‘intermediate’ (beige or brite adipose, hereafter referred to as beige) adipose tissue in these regions [15] Further studies of these fat depots have revealed distinct genetic markers that may aid distinction of the different sub-classes of adipocytes in humans [16,17,18,19]. Rodent WAT depots, have variable capacities to form beige fat, expressing high levels of BAT gene and protein markers after prolonged cold or adrenergic pharmacological stimulation [21,22,23]. The degree to which, the considerable volume of human subcutaneous WAT can form beige fat, whether by transdifferentiation or de novo production from precursor cells, is of importance to future therapeutic strategies for obesity
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