Background & Aims: Obesity and related co-morbidities such as non-alcoholic fatty liver disease (NAFLD)
are increasing dramatically worldwide. Genetic variations in the gene encoding Patatin-like
phospholipase domain-containing protein 3 (PNPLA3) which is also known as adiponutrin
(ADPN) have been associated with NAFLD affecting hepatic fat content and liver inflammation
yet the underlying molecular mechanisms remain unknown. The aim of our study was to
investigate whether weight loss affects both hepatic and adipose PNPLA3 expression
in severely obese patients before and after laparoscopic gastric banding (LAGB).
Methods: Liver and subcutaneous adipose tissue samples were collected from twenty severely
obese patients before and 6 months after LAGB. PNPLA3 expressions were assessed by
quantitative real-time PCR. To understand whether inflammatory signals affected PNPLA3
expression, we additionally performed in vitro experiments to study the effect of
lipopolysaccharide (LPS) and tumour necrosis factor alpha (TNFα) on PNPLA3 expression
in primary CD14+ monocytes, SGBS adipocytes, and Hep3b hepatoma cells.
Results: PNPLA3 expression was stronger (about 9-fold) in the liver but also clearly detectable
in subcutaneous adipose tissue. Hepatic PNPLA3 expression remained unaffected by weight
loss. In contrast and surprisingly, PNPLA3 expression was increased in subcutaneous
adipose tissue 6 months after LAGB. Concordantly, LPS and TNFα abolished PNPLA3 expression
in monocytes and the latter also reduced PNPLA3 expression in adipocytes, but not
Hep3b hepatocytes.
Conclusions: Our data demonstrate that adipose tissue, but not hepatic PNPLA3 expression, is restored
by LAGB-induced weight loss. Thus, we suggest that it might be worthwhile to address
the impact of PNPLA3 and its role in in the adipose tissue in future experimental
studies.
