Figure 3. Age-dependent decline in homeostatic adipogenesis in human SAT.

(A) ²H-labeled and unlabeled adipocyte nuclei after 4-week ²H-water–labeling pulse and 6-month chase. The ²H/¹H HSI image (top right) shows label localized to the nucleus of a putative new adipocyte (arrows), in contrast to the unlabeled nucleus (bottom right, arrows). Scale ranges from background natural abundance to 100% (or 2 times) background. Scale bar: 5 μm. (B) Schematic depicting the hypothesized labeling of an adipocyte that matures during ²H-water labeling. ²H-labeling is expected to be high due to the developmental surge in lipid storage that occurs when a progenitor differentiates into a mature lipid-storing adipocyte. Prior analyses of the fate of ²H-water have established incorporation of ²H atoms by enzymatic reactions involved in pathways of intermediate metabolism, including gluconeogenesis, glycolysis, and the TCA cycle, thereby leading to the labeling of both the glycerol and fatty acid precursors of triglycerides. (C) ²H-high adipocyte lipid droplet (arrows). A small subset of such cells persisted after 6-month chase. (D) Correlation between the frequency of ²H-labeled adipocyte nuclei as shown in A and ²H-high adipocyte lipid droplets as shown in C at the 6-month chase time point (n = 9 subjects). (E) Negative correlation between projected adipocyte birth rate and subject age demonstrated for both measurements of new adipocyte formation (²H-labeled adipocyte nuclei and ²H-high adipocyte lipid droplets) (n = 9 subjects). (F) Positive correlation between projected yearly adipocyte birth rates and serum IGF-1 levels at 6-month chase time point (n = 9 subjects). (D–F) Data obtained by univariate regression.