NanoSIMS imaging reveals unexpected heterogeneity in nutrient uptake by brown adipocytes

Abstract

Heterogeneity in the metabolic properties of adipocytes in white adipose tissue has been well documented. We sought to investigate metabolic heterogeneity in adipocytes of brown adipose tissue (BAT), focusing on heterogeneity in nutrient uptake. To explore the possibility of metabolic heterogeneity in brown adipocytes, we used nanoscale secondary ion mass spectrometry (NanoSIMS) to quantify uptake of lipids in adipocytes interscapular BAT and perivascular adipose tissue (PVAT) after an intravenous injection of triglyceride-rich lipoproteins (TRLs) containing [²H]triglycerides (²H-TRLs). The uptake of deuterated lipids into brown adipocytes was quantified by NanoSIMS. We also examined ¹³C enrichment in brown adipocytes after administering [¹³C]glucose or ¹³C-labeled mixed fatty acids by gastric gavage. The uptake of ²H-TRLs-derived lipids into brown adipocytes was heterogeneous, with ²H enrichment in adjacent adipocytes varying by more than fourfold. We also observed substantial heterogeneity in ¹³C enrichment in adjacent brown adipocytes after administering [¹³C]glucose or [¹³C]fatty acids by gastric gavage. The uptake of nutrients by adjacent brown adipocytes within a single depot is variable, suggesting that there is heterogeneity in the metabolic properties of brown adipocytes.

Keywords: Brown adipose tissue; Fatty acids; NanoSIMS imaging; Nutrient uptake; White adipose tissue.