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bioRxiv · 10.1101/853184

14-3-3ζ over-expression improves tolerance to acute and chronic cold exposure in male mice via thermogenic-dependent and -independent mechanisms

Diallo, K.·Dussault, S.·Lopez, A. F.·Rivard, A.·Lim, G.
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Abstract

Following prolonged cold exposure, adaptive thermogenic pathways are activated to maintain homeothermy, and elevations in body temperature are generally associated with UCP1-dependent and -independent increases in energy expenditure. One of the earliest, identified functions of the molecular scaffold, 14-3-3{zeta}, was its role in the synthesis of norepinephrine, a key endogenous factor that stimulates thermogenesis. This suggests that 14-3-3{zeta} may have critical roles in cold-induced thermogenesis. Herein, we report that transgenic over-expression of TAP-14-3-3{zeta} in mice significantly improved tolerance to prolonged cold. When compared to wildtype controls, TAP mice displayed significantly elevated body temperatures and paradoxical decreases in energy expenditure. No changes in {beta}-adrenergic sensitivity or oxidative metabolism were observed; instead, 14-3-3{zeta} over-expression significantly decreased thermal conductance via increased peripheral vasoconstriction. These findings suggest 14-3-3{zeta} mediates alternative, non-thermogenic mechanisms to mitigate heat loss for homeothermy. Our results point to an unexpected role of 14-3-3{zeta} in the regulation of body temperature. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=137 HEIGHT=200 SRC="FIGDIR/small/853184v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1f5b454org.highwire.dtl.DTLVardef@1219a7org.highwire.dtl.DTLVardef@523fb3org.highwire.dtl.DTLVardef@1d41780_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Diallo, K., Dussault, S., Lopez, A. F., Rivard, A., Lim, G.. 2019-11-24. 14-3-3ζ over-expression improves tolerance to acute and chronic cold exposure in male mice via thermogenic-dependent and -independent mechanisms. https://doi.org/10.1101/853184

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