Conclusions
PRDM16 is a key transcriptional regulator in beige adipocyte
formation and can stimulate nearly all key characteristics of authentic
brown fat cells 26. In addition, althoughPRDM16 is introduced before cell differentiation, nearly all
adipocytes can be activated to
express BAT-selective genes [17]. In this study, we found that
BAT-selective genes were up-regulated in PRDM16-overexpressing 3T3-L1
cells compared with the control group, indicating that the mutation inPRDM16 influences the function of this gene in the brown
adipogenesis program. PRDM16 regulates thermogenic genes by forming a
complex with various transcription factors, includingC/EBPβ ,PGC-1α , PPARα and PPARγ . Although the same
differentiation efficiency was induced, the suppression of C/EBPβand PGC-1α mRNA expression levels in the PRDM16 MU group
indicated a decreased formation of the transcription complex and
finally, the suppression of the expression of thermogenic genes, such asUCP1 , compared with the PRDM16 group. Functional differences in
PRDM16 caused by sequence variations could explain why northern cattle
are more cold-tolerant than southern cattle. For example, mortality forB. indicus is suggested to be higher than that for B.
taurus in the cold [47], which may be a result of exhausting their
post-natal BAT lipids [48].
Therefore,
on one hand, PRDM16 functioned well in northern cattle is
required to resist extreme cold, and on the another hand, the functional
inactivation of PRDM16 impairs beige adipocyte formation, which is also
beneficial for the environment adaptability of southern cattle. In
summary, we compared the whole genomes of northern cattle living in
extremely cold environments with those of southern cattle living in warm
environments to reveal a new mechanism behind northern cattle’s
adaptability to cold environments. This study is the first to propose a
molecular mechanism for cattle’s cold-tolerance ability. In particular,
we proved that PRDM16 is a forceful genome effector that
facilitates the formation of diverse cold-adaptations using functional
experiments.
These
results could improve the comprehension of adaptive genetic variations
in cattle living in different temperatures and other livestock species.