**5. Conclusions**

By carrying out our studies under conditions where thermal stress was eliminated, we have highlighted the protective role of UCP3 against ectopic lipid accumulation in lean tissues. Of relevance, by varying the energy and fat intake through the administration of HFD, the role that is played by UCP3 in contrasting HFD-induced fat accumulation clearly emerged. In addition, results that were obtained from studies performed in animals housed at thermoneutrality could be better translated to humans, which choose to live in a thermoneutral environment.

**Author Contributions:** A.L. (Assunta Lombardi), F.G., M.M. and A.L. (Antonia Lanni); Conceptualization. A.L. (Assunta Lombardi), R.A.B., R.d.M., L.L., S.S., A.G., E.S., F.C., P.d.L. and R.S.; investigation and data curation, A.L. (Assunta Lombardi), F.G.; original draft preparation; A.L. (Assunta Lombardi), F.G., M.M., L.L., A.L. (Antonia Lanni), P.d.L., E.S., R.D.M. and L.L.; review and editing manuscript.

**Funding:** This work was supported by University of Sannio (Fondi FRA 2016) and by Department of Biology University of Naples Federico II (Ricerca di Base).

**Conflicts of Interest:** The authors declare no conflict of interest.
