diabetes-2019-keynote

2 / 3

Page 11
Joint Event
November 29-30, 2019 | Frankfurt, Germany
28th International Conference on 3rd International Conference on
Diabetes and Endocrinology Diabetes and Metabolism &
2
0
1
9 CONGRESS
DIABETES
2019
DIABETES
Journal of Endocrine Disorders & Surgery | Volume 3
Hepatic metabolism and elimination of endobiotics (e.g.,
steroids, bile acids) and xenobiotics (e.g., drugs, toxins)
is essential for health. While the enzymatic (termed phase
I-II) and transport machinery (termed phase III) controlling
endobiotic and xenobiotic metabolism (EXM) is known, our
understanding of molecular nodal points that coordinate
EXM function in physiology and disease remains incompletely
understood. Here we show that the transcription factor
Kruppel-like factor 15 (KLF15) regulates all three phases of
the EXM system by direct and indirect pathways. Unbiased
transcriptomicanalysescoupledwithvalidationstudiesincells,
human tissues, and animals, support direct transcriptional
control of the EXM machinery by KLF15. Liver-specific
deficiency of KLF15 (Li-KO) results in altered expression of
numerous phase I-III targets, and renders animals resistant to
the pathologic effect of bile acid and acetaminophen toxicity.
Furthermore, Li-KO mice demonstrate enhanced degradation
and elimination of endogenous steroid hormones, such
as testosterone and glucocorticoid, resulting in reduced
male fertility and blood glucose level, respectively. Viral
reconstitution of hepatic KLF15 expression in Li-KO mice
reverses these phenotypes. Our observations identify a
previously unappreciated transcriptional pathway regulating
metabolism and elimination of endobiotics and xenobiotics.
Figure 1. Schematic of KLF15-dependent regulation of EXM machinery
and associated functions.
Speaker Biography
Shuxin Han has been engaged in metabolic biology research for nearly 15
years. Dr. Han mainly studies the transcriptional regulation of metabolism
by various transcription factors from previously nuclear receptors to
currentlykruppel-likefactor(KLF)family.Hisrecentacademicachievements
include three parts. First, Dr. Han opens a new research area of the KLF
family regulation of endobiotic and xenobioticmetabolism. Second, Dr. Han
discovers a novel patent therapeutic target for several human diseases such
as liver injury and infertility. Third, Dr. Han expands and deepens the field
of surgery metabolism.
e:
Shuxin Han
Case Western Reserve University, USA
KLF15 regulates endobiotic and xenobiotic metabolism
Notes: