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SUMMARY:TIP60-mediated lipin 1 acetylation links fatty acid sensing to adi
 posity
DTSTART:20170424T103000
DTEND:20170424T113000
DTSTAMP:20260506T143955Z
UID:94920a09c185225bbb1c3b28033519f59004b0eb20a86bebdccd5054
CATEGORIES:Conferences - Seminars
DESCRIPTION:Yang Li\, Xiamen University
\, Fujian Province\, China\nSEMI
 NAR of the LAUSANNE INTEGRATIVE METABOLISM and NUTRITION ALLIANCE (LIMNA)\
 n\nAbstract:\nObesity is characterized by excessive fatty acid (FA) conver
 sion to triacylglycerol (TAG) and fat accumulation in adipose tissues\, af
 flicting a large population worldwide. However\, how signaling networks se
 nse FAs and connect to the stimulation of lipid synthesis is poorly unders
 tood. Here\, we show that homozygous knock-in mice carrying a single point
  mutation of acetyltransferase Tip60 at the Ser86 phosphorylation site (Ti
 p60S86A) display 40-60% reductions of body fat mass. In addition\, the Tip
 60S86A mice are virtually immune to high-fat diet (HFD)-induced obesity an
 d metabolic disorders such as hepatosteatosis and insulin resistance. Mech
 anistically\, upon HFD or FA treatment\, TIP60 is hyperphosphorylated at S
 er86\, as a result of the inherent inhibition of AKT signaling by FA\, enh
 ancing the acetyltransferase activity of TIP60. Activated TIP60 then direc
 tly interacts and acetylates the phosphatidic acid (PA) phosphatase lipin 
 1\, which catalyzes the dephosphorylation of PA to diacylglycerol (DAG)\, 
 the penultimate step in TAG biosynthesis.\n\nWe have also identified Lys42
 5 and Lys595 residues in lipin 1 as the TIP60-dependent acetylation sites.
  After acetylation\, lipin 1 translocates from cytosol to endoplasmic reti
 culum (ER)-associated membranes\, allowing for the production of neutral l
 ipids therein. An acetylation-defective K425/595R mutant of lipin 1 failed
  to rescue lipin 1-dependent TAG synthesis in CRISPR/Cas9-mediated LPIN1 k
 nockout cells.\n\nThese results highlight a gate-keeping role of TIP60 as 
 well as lipin 1 acetylation in lipid synthesis\, and proper modulation of 
 TIP60 activity might be a promising strategy for the alleviation of obesit
 y.\n 
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717
STATUS:CONFIRMED
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