Hepatic Steatosis and Ectopic Fat Are Associated With Differences in Subcutaneous Adipose Tissue Gene Expression in People With HIV.
Curtis L GabrielFei YeRun FanSangeeta NairJames G TerryJohn Jeffrey CarrHeidi SilverPaxton BakerLaToya HannahCelestine WanjallaMona MashayekhiSam BailinMorgan LimaBeverly WoodwardManhal J IzzyJane F FergusonJohn R KoethePublished in: Hepatology communications (2021)
Persons with human immunodeficiency virus (PWH) have subcutaneous adipose tissue (SAT) dysfunction related to antiretroviral therapy and direct viral effects, which may contribute to a higher risk of nonalcoholic fatty liver disease compared with human immunodeficiency virus-negative individuals. We assessed relationships between SAT expression of major adipocyte regulatory and lipid storage genes with hepatic and other ectopic lipid deposits in PWH. We enrolled 97 PWH on long-term antiretroviral therapy with suppressed plasma viremia and performed computed tomography measurements of liver attenuation, a measure of hepatic steatosis, skeletal muscle (SM) attenuation, and the volume of abdominal subcutaneous, visceral, and pericardial adipose tissue. Whole SAT gene expression was measured using the Nanostring platform, and relationships with computed tomography imaging and fasting lipids were assessed using multivariable linear regression and network mapping. The cohort had a mean age of 47 years, body mass index of 33.4 kg/m2, and CD4 count of 492 cells/mm3. Lower liver attenuation, a marker of greater steatosis, was associated with differences in SAT gene expression, including lower lipoprotein lipase and acyl-CoA dehydrogenase, and higher phospholipid transfer protein. Lower liver attenuation clustered with lower visceral adipose tissue (VAT) attenuation and greater VAT volume, pericardial fat volume and triglycerides, but no relationship was observed between liver attenuation and SAT volume, SM attenuation, or low-density lipoprotein. Conclusion: Liver attenuation was associated with altered SAT expression of genes regulating lipid metabolism and storage, suggesting that SAT dysfunction may contribute to nonalcoholic fatty liver disease in PWH. SAT gene-expression relationships were similar for VAT volume and attenuation, but not SM, indicating that ectopic lipid deposition may involve multiple pathways.
Keyphrases
- human immunodeficiency virus
- adipose tissue
- antiretroviral therapy
- gene expression
- insulin resistance
- hiv infected
- fatty acid
- hiv positive
- hepatitis c virus
- high fat diet
- computed tomography
- hiv aids
- skeletal muscle
- hiv infected patients
- body mass index
- dna methylation
- high resolution
- genome wide
- magnetic resonance imaging
- poor prognosis
- oxidative stress
- blood pressure
- low density lipoprotein
- magnetic resonance
- high fat diet induced
- induced apoptosis
- cell death
- positron emission tomography
- type diabetes
- south africa
- transcription factor
- signaling pathway
- binding protein