Figure 5.

Suppression of fatty acid biosynthesis selectively in brown adipocytes does not affect SNS expansion in BAT or the number of multilocular cells in iWAT at thermoneutrality. (A) Western blot for detection of TH, UCP1 and tubulin protein in BAT from control, iUCP1-Cre-FASNKO mice housed at thermoneutrality and treated or not with CL316,243. (B) Quantifications of TH (B) and UCP1 (C) protein levels in BAT upon induction of adipocyte FASN deletion. TH protein levels were quantified by densitometry from immunoblot data shown in (A). (D) Immunohistochemistry (IHC) for detection of Tyrosine hydroxylase (TH) contents in BAT from control mice or UCP1-Cre-FANSKO mice housed at thermoneutrality. (E) q-PCR was performed for quantifications of indicated genes in iWAT from controls and iUCP1-Cre-FASNKO mice housed at 30 °C and treated or not with CL316,243 for 6 days. (F) Proposed model showing how disruption of adipocyte DNL pathway through FASN knockout stimulates adipose neuronal activity and thermogenic program. Accordingly, adipocyte FASN deletion enhances the levels of intermediate lipids acetyl-CoA and malonyl-CoA (green arrows), but reduces palmitate (red arrows). Such changes trigger the production of neurotropic factors and signals conveyed to the brain, enhancing the adipose sympathetic outflow. Graphs show the mean +/− SEM. N = 5–7 mice per group. *P < 0.05; ****P < 0.0001.