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7
t h
E u r o p e a n C o n g r e s s o n
Obesity and
Eating Disorder
Obesity 2018
Journal of Obesity & Eating Disorders
ISSN 2471-8203
A p r i l 1 2 - 1 3 , 2 0 1 8
Am s t e r d a m , N e t h e r l a n d s
Page 26
O
besity is characterized by excessive body fat accumulation stored as
triacylglycerol (TAG) in adipose lipid droplets, and the breakdown of stored
TAG is stimulated by food deprivation (fasting) or stress. Sympathetic nerve
activation enhances lipolysis in adipocytes, a process of which is regulated
by phosphorylation of hormone sensitive lipase (HSL) and perilipin. We
have elucidated that phospholipase C-related catalytically inactive protein
(
PRIP
), a binding partner of protein phosphatase 1 (PP1) and 2A (PP2A),
modulates the lipolysis process in adipose tissues and regulates adiposity and
thermogenesis.
PRIP
was originally identified as an inositol 1, 4, 5-trisphosphate
binding protein and a phosphatideylinositol 4, 5-bisphosphate through its
pleckstrin homology domain.
PRIP
is similar to phospholipase C-δ1 but lacks
enzymatic activity.
Prip
-knockout (KO) mice showed a lean phenotype. The
phosphorylation levels of HSL and perilipin were greater in white adipose
tissue (WAT) prepared from regular diet-fed or fasted
Prip
-KO mice than those
in wild-type mice, suggesting enhanced lipolytic activity in
Prip
-KO WAT. In
response to adrenaline stimulation,
PRIP
and protein phosphatases, PP1 and
PP2A, translocated onto lipid droplets in
Prip
-KO adipocytes, which enhanced
dephosphorylation of HSL followed by the inhibition of non-esterified fatty
acid and glycerol production. The upregulation of lipolytic activity was also
observed in
Prip
-KO brown adipose tissue (BAT). Furthermore,
Prip
-KO BAT
displayed increased expression of uncoupling protein 1 (UCP1). Consistently,
a high-fat diet (HFD)-fed
Prip
-KO mice showed increased energy expenditure, a
high rectal temperature, and a lean phenotype compared with control wild-type
mice. Collectively,
PRIP
is a novel molecule that regulates fat metabolism and
thermogenesis.
Biography
Takashi Kanematsu received his PhD in Biochemistry from
Kyushu University, Fukuoka Japan, in 1994. He then worked
as a Postdoctoral Fellow at Vanderbilt University, TN USA, and,
subsequently, served as Assistant and Associate Professor in
the Department of Biochemistry at Kyushu University (1997–
2008). From 2009, he is Professor and Chair of the Department
of Cellular and Molecular Pharmacology at Hiroshima Universi-
ty, Hiroshima Japan. He currently serves on the Editorial Board
of
Journal of Pharmacological Sciences.
tkanema2@hiroshima-u.ac.jpPhospholipase C-related catalytically inactive protein regulates fat
metabolism and energy expenditure
Takashi Kanematsu, Kana Oue, Yosuke Yamawaki and
Satoshi Asano
Hiroshima University, Japan
Takashi Kanematsu et al., J Obes Eat Disord 2018, Volume: 4
DOI: 10.21767/2471-8203-C1-008