Patatin-like phosphatase domain-containing 3 genotype and quality of dietary fat modify the liver adiposity

Background Patatin-like phosphatase domain-containing 3 ( PNPLA3 ) gene and dietary fat are important factors for metabolic dysfunction-associated steatotic liver disease (MASLD). Objective We studied the impact of dietary fat quality modification on liver adiposity in men homozygotes for PNPLA3 (GG, carriers of the risk allele and CC, non-carriers). Methods Ninety-eight men (age: 67.8 ± 4.2 years, body mass index: 27.2 ± 2.5 kg/m ² ), homozygous for PNPLA3 rs738409 variant (I148M), randomly assigned for two diet intervention arms, participated in a 12-week diet intervention. Recommended diet (RD) arm ate fat according to the National and Nordic nutrition recommendations, average diet (AD) arm ate according to the average fat intake in Finland. Liver imaging by ultrasound with 2D-shear wave elastography (2D-SWE) and magnetic resonance imaging (MRI) in combination with magnetic resonance spectroscopy (MRS) were performed. Results MRI-based liver fat proportion decreased in the RD arm (CC: from 3.8 ± 3.2% to 3.2 ± 3.3%, GG: from 3.9 ± 3.3% to 3.5 ± 3.1%, p time  = 0.032) and increased in the AD arm (CC: from 4.1 ± 3.6% to 4.8 ± 3.9%, GG: from 4.7 ± 3.7% to 6.7 ± 5.3%, p time  = 0.015). MRS-quantified liver saturated fat content increased in the AD arm in both genotypes of PNPLA3 ( p time  = 0.010). Liver triglyceride concentration did not change in either arm with the CC genotype but increased in the AD arm with the GG genotype (for time and genotype interaction p  = 0.027). Conclusion Diet based on fat quality recommendations could be beneficial for liver health in both PNPLA3 genotypes CC and GG. The average diet seems to be especially harmful for liver health in carriers of the PNPLA3 risk genotype (GG).