The PNPLA3-I148M Variant Confers an Antiatherogenic Lipid Profile in Insulin-resistant Patients
| Autor: | Panu K. Luukkonen, Anne Juuti, Marju Orho-Melander, Anne K. Penttilä, Sami Qadri, Henna Sammalkorpi, Tiina Lehtimäki, Johanna Arola, Hannele Yki-Järvinen, Antti Hakkarainen |
|---|---|
| Přispěvatelé: | HUS Internal Medicine and Rehabilitation, Department of Medicine, Clinicum, Doctoral Programme in Clinical Research, Department of Diagnostics and Therapeutics, HUS Medical Imaging Center, Helsinki University Hospital Area, HUS Abdominal Center, Department of Surgery, Department of Pathology, Hannele Yki-Järvinen Research Group |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Very low-density lipoprotein Steatosis Endocrinology Diabetes and Metabolism Clinical Biochemistry Biochemistry Lipoprotein particle Cohort Studies 0302 clinical medicine Endocrinology Methionine insulin resistance rasvamaksatauti genetics metabolinen oireyhtymä aineenvaihdunta Finland Disease Resistance 2. Zero hunger 0303 health sciences medicine.diagnostic_test rasvamaksa Middle Aged 3. Good health Liver biopsy 030211 gastroenterology & hepatology Female non-alcoholic fatty liver Adult medicine.medical_specialty ateroskleroosi genetiikka ei-alkoholiperäinen rasvamaksatauti lipoproteiinit Polymorphism Single Nucleotide metabolic syndrome TM6SF2 steatoosi 03 medical and health sciences Insulin resistance Internal medicine NAFLD metabolia medicine Humans Isoleucine Genetic Association Studies PNPLA3 030304 developmental biology fatty liver business.industry Biochemistry (medical) dyslipidemia Membrane Proteins non-alcoholic fatty liver disease Lipase medicine.disease Lipid Metabolism insuliiniresistenssi patatin-like phospholipase domain containing 3 lipoproteins Cross-Sectional Studies Amino Acid Substitution 3121 General medicine internal medicine and other clinical medicine Lipidomics fatty liver disease Metabolic syndrome atherosclerosis business Lipid profile Body mass index metabolism Lipoprotein |
| Popis: | 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 49 ± 9 years, body mass index [BMI] 43.2 ± 6.8 kg/m2), and 345 less obese volunteers in whom liver fat was measured by proton magnetic resonance spectroscopy (nonbariatric cohort: age 45 ± 14 years, BMI 29.7 ± 5.7 kg/m2). Main Outcome Measures 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|