The PNPLA3-I148M Variant Confers an Antiatherogenic Lipid Profile in Insulin-resistant Patients.
J Clin Endocrinol Metab
; 106(1): e300-e315, 2021 01 01.
Article
in En
| MEDLINE
| ID: mdl-33064150
ABSTRACT
CONTEXT The I148M (rs738409-G) variant in PNPLA3 increases liver fat content but may be protective against cardiovascular disease. Insulin resistance (IR) amplifies the effect of PNPLA3-I148M on liver fat. OBJECTIVE:
To study whether PNPLA3-I148M confers an antihyperlipidemic effect in insulin-resistant patients.DESIGN:
Cross-sectional study comparing the impact of PNPLA3-I148M on plasma lipids and lipoproteins in 2 cohorts, both divided into groups based on rs738409-G allele carrier status and median HOMA-IR.SETTING:
Tertiary referral center. PATIENTS A total of 298 obese patients who underwent a liver biopsy during bariatric surgery (bariatric cohort age 49â ±â 9 years, body mass index [BMI] 43.2â ±â 6.8 kg/m2), and 345 less obese volunteers in whom liver fat was measured by proton magnetic resonance spectroscopy (nonbariatric cohort age 45â ±â 14 years, BMI 29.7â ±â 5.7 kg/m2). MAIN OUTCOMEMEASURES:
Nuclear magnetic resonance profiling of plasma lipids, lipoprotein particle subclasses and their composition.RESULTS:
In both cohorts, individuals carrying the PNPLA3-I148M variant had significantly higher liver fat content than noncarriers. In insulin-resistant and homozygous carriers, PNPLA3-I148M exerted a distinct antihyperlipidemic effect with decreased very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) particles and their constituents, and increased high-density lipoprotein particles and their constituents, compared with noncarriers. VLDL particles were smaller and LDL particles larger in PNPLA3-I148M carriers. These changes were geometrically opposite to those due to IR. PNPLA3-I148M did not have a measurable effect in patients with lower IR, and its effect was smaller albeit still significant in the less obese than in the obese cohort.CONCLUSIONS:
PNPLA3-I148M confers an antiatherogenic plasma lipid profile particularly in insulin-resistant individuals.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Insulin Resistance
/
Atherosclerosis
/
Disease Resistance
/
Lipase
/
Membrane Proteins
Type of study:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
En
Journal:
J Clin Endocrinol Metab
Year:
2021
Document type:
Article
Affiliation country:
Finlandia