Endogenous Omega-3 Polyunsaturated Fatty Acids Reduce the Number and Differentiation of White Adipocyte Progenitors in Mice.

OBJECTIVES: Reducing the increased number of white adipocyte progenitors (WAP) is considered a novel approach to controlling obesity. The role of omega-3 polyunsaturated fatty acids (PUFA) in regulating the WAP resident population is unclear. The objective of this study was to investigate the effect of omega-3 PUFA on the niche composition of adipose-derived stem cells. METHODS: Stromal vascular cell fraction (SVF) was collected from subcutaneous fat of wild-type (WT) and transgenic mice carrying a fat-1 gene from Caenorhabditis elegans (Fat-1 mice), which are capable of synthesizing omega-3 PUFA and have much higher tissue levels of omega-3 PUFA relative to WT mice. The isolated SVF cells were cultured and used for the examination of adipocyte differentiation, adipogenic markers, fatty acid composition, and WAP numbers. RESULTS: SVF isolated from Fat-1 mice (Fat-1-SVF) exhibited markedly fewer differentiated adipocytes with smaller cell size and less lipid content than that of WT mice (WT-SVF). Accordingly, adipogenesis-related genes and the white adipocyte surface marker ASC-1 were downregulated in Fat-1-SVF relative to WT-SVF. Furthermore, WAP numbers and adipose tissue macrophages were lower in Fat-1-SVF than WT-SVF. CONCLUSIONS: Omega-3 PUFA can both limit the WAP resident population and suppress their differentiation to white adipocytes, suggesting a new mechanism for the antiobesity effect of omega-3 PUFA.