Abstract
We examined whether relative concentrations of
circulating triacylglycerols (TAGs) between carriers
compared with noncarriers of PNPLA3I148M gene variant
display deficiency of TAGs, which accumulate in the liver
because of defective lipase activity. We also analyzed
the effects of obesity-associated nonalcoholic fatty
liver disease (NAFLD) independent of genotype, and of
NAFLD due to either PNPLA3I148M gene variant or obesity
on circulating TAGs. A total of 372 subjects were divided
into groups based on PNPLA3 genotype or obesity. Absolute
and relative deficiency of distinct circulating TAGs was
observed in the PNPLA3148MM/148MI compared with the
PNPLA3 148II group. Obese and 'nonobese' groups had
similar PNPLA3 genotypes, but the obese subjects were
insulinresistant. Liver fat was similarly increased in
obese and PNPLA3148MM/148MI groups. Relative
concentrations of TAGs in the obese subjects versus
nonobese displayed multiple changes. These closely
resembled those between obese subjects with NAFLD but
without PNPLA3I148M versus those with the I148M variant
and NAFLD. The etiology of NAFLD influences circulating
TAG profiles. 'PNPLA3 NAFLD' is associated with a
relative deficiency of TAGs, supporting the idea that the
I148M variant impedes intrahepatocellular lipolysis
rather than stimulates TAG synthesis. 'Obese NAFLD' is
associated with multiple changes in TAGs, which can be
attributed to obesity/insulin resistance rather than
increased liver fat content per se
Original language | English |
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Pages (from-to) | 312-322 |
Journal | Diabetes |
Volume | 63 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2014 |
MoE publication type | A1 Journal article-refereed |