Reduced adipogenic gene expression in thigh adipose tissue precedes human immunodeficiency virus-associated lipoatrophy

Mario Kratz, Jonathan Purnell, Patricia A. Breen, Katherine K. Thomas, Kristina M. Utzschneider, Darcy B. Carr, Steven E. Kahn, James P. Hughes, Elizabeth A. Rutledge, Brian Van Yserloo, Michi Yukawa, David S. Weigle

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Context: The expression of adipogenic genes in sc adipose tissue has been reported to be lower among patients with HIV-associated lipoatrophy than HIV-uninfected controls. It is unclear whether this is a result or cause of lipoatrophy. Objective: The objective of the study was to investigate the temporal relationships among changes in adipogenic gene expression in sc adipose tissue and changes in body fat distribution and metabolic complications in HIV-infected subjects on antiretroviral therapy. Design: This was a prospective longitudinal study. Setting: The study was conducted at HIV clinics in Seattle, Washington. Participants: The study population included 31 HIV-infected and 12 control subjects. Interventions: Subjects were followed up for 12 months after they initiated or modified their existing antiretroviral regimen. Main Outcome Measures: Changes in body composition, plasma lipids, insulin sensitivity, and gene expression in sc abdominal and thigh adipose tissue. Results: Subjects who developed lipoatrophy (n = 10) had elevated fasting triglycerides [3.16 (SD 2.79) mmol/liter] and reduced insulin sensitivity as measured by frequently sampled iv glucose tolerance test [1.89 (SD 1.27) × 10-4 min-1/μU·ml] after 12 months, whereas those without lipoatrophy (n = 21) did not show any metabolic complications [triglycerides 1.32 (SD 0.58) mmol/liter, P = 0.01 vs. lipoatrophy; insulin sensitivity 3.52 (SD 1.91) × 10-4 min-1/μU·ml, P = 0.01 vs. lipoatrophy]. In subjects developing lipoatrophy, the expression of genes involved in adipocyte differentiation, lipid uptake, and local cortisol production in thigh adipose tissue was significantly reduced already at the 2-month visit, several months before any loss of extremity fat mass was evident. Conclusions: In HIV-infected subjects, lipoatrophy is associated with elevated fasting triglycerides and insulin resistance and might be caused by a direct or indirect effect of antiretroviral drugs on sc adipocyte differentiation.

Original languageEnglish (US)
Pages (from-to)959-966
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume93
Issue number3
DOIs
StatePublished - Mar 2008

Fingerprint

Thigh
Viruses
Gene expression
Adipose Tissue
HIV
Insulin
Tissue
Gene Expression
Triglycerides
Insulin Resistance
Genes
Fats
Lipids
Adipocytes
Fasting
Body Fat Distribution
Hydrocortisone
Abdominal Fat
Glucose Tolerance Test
Body Composition

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Reduced adipogenic gene expression in thigh adipose tissue precedes human immunodeficiency virus-associated lipoatrophy. / Kratz, Mario; Purnell, Jonathan; Breen, Patricia A.; Thomas, Katherine K.; Utzschneider, Kristina M.; Carr, Darcy B.; Kahn, Steven E.; Hughes, James P.; Rutledge, Elizabeth A.; Van Yserloo, Brian; Yukawa, Michi; Weigle, David S.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 93, No. 3, 03.2008, p. 959-966.

Research output: Contribution to journalArticle

Kratz, M, Purnell, J, Breen, PA, Thomas, KK, Utzschneider, KM, Carr, DB, Kahn, SE, Hughes, JP, Rutledge, EA, Van Yserloo, B, Yukawa, M & Weigle, DS 2008, 'Reduced adipogenic gene expression in thigh adipose tissue precedes human immunodeficiency virus-associated lipoatrophy', Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 3, pp. 959-966. https://doi.org/10.1210/jc.2007-0197
Kratz, Mario ; Purnell, Jonathan ; Breen, Patricia A. ; Thomas, Katherine K. ; Utzschneider, Kristina M. ; Carr, Darcy B. ; Kahn, Steven E. ; Hughes, James P. ; Rutledge, Elizabeth A. ; Van Yserloo, Brian ; Yukawa, Michi ; Weigle, David S. / Reduced adipogenic gene expression in thigh adipose tissue precedes human immunodeficiency virus-associated lipoatrophy. In: Journal of Clinical Endocrinology and Metabolism. 2008 ; Vol. 93, No. 3. pp. 959-966.
@article{b1809fc2a56a49a089ff08bb6ea6641c,
title = "Reduced adipogenic gene expression in thigh adipose tissue precedes human immunodeficiency virus-associated lipoatrophy",
abstract = "Context: The expression of adipogenic genes in sc adipose tissue has been reported to be lower among patients with HIV-associated lipoatrophy than HIV-uninfected controls. It is unclear whether this is a result or cause of lipoatrophy. Objective: The objective of the study was to investigate the temporal relationships among changes in adipogenic gene expression in sc adipose tissue and changes in body fat distribution and metabolic complications in HIV-infected subjects on antiretroviral therapy. Design: This was a prospective longitudinal study. Setting: The study was conducted at HIV clinics in Seattle, Washington. Participants: The study population included 31 HIV-infected and 12 control subjects. Interventions: Subjects were followed up for 12 months after they initiated or modified their existing antiretroviral regimen. Main Outcome Measures: Changes in body composition, plasma lipids, insulin sensitivity, and gene expression in sc abdominal and thigh adipose tissue. Results: Subjects who developed lipoatrophy (n = 10) had elevated fasting triglycerides [3.16 (SD 2.79) mmol/liter] and reduced insulin sensitivity as measured by frequently sampled iv glucose tolerance test [1.89 (SD 1.27) × 10-4 min-1/μU·ml] after 12 months, whereas those without lipoatrophy (n = 21) did not show any metabolic complications [triglycerides 1.32 (SD 0.58) mmol/liter, P = 0.01 vs. lipoatrophy; insulin sensitivity 3.52 (SD 1.91) × 10-4 min-1/μU·ml, P = 0.01 vs. lipoatrophy]. In subjects developing lipoatrophy, the expression of genes involved in adipocyte differentiation, lipid uptake, and local cortisol production in thigh adipose tissue was significantly reduced already at the 2-month visit, several months before any loss of extremity fat mass was evident. Conclusions: In HIV-infected subjects, lipoatrophy is associated with elevated fasting triglycerides and insulin resistance and might be caused by a direct or indirect effect of antiretroviral drugs on sc adipocyte differentiation.",
author = "Mario Kratz and Jonathan Purnell and Breen, {Patricia A.} and Thomas, {Katherine K.} and Utzschneider, {Kristina M.} and Carr, {Darcy B.} and Kahn, {Steven E.} and Hughes, {James P.} and Rutledge, {Elizabeth A.} and {Van Yserloo}, Brian and Michi Yukawa and Weigle, {David S.}",
year = "2008",
month = "3",
doi = "10.1210/jc.2007-0197",
language = "English (US)",
volume = "93",
pages = "959--966",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "3",

}

TY - JOUR

T1 - Reduced adipogenic gene expression in thigh adipose tissue precedes human immunodeficiency virus-associated lipoatrophy

AU - Kratz, Mario

AU - Purnell, Jonathan

AU - Breen, Patricia A.

AU - Thomas, Katherine K.

AU - Utzschneider, Kristina M.

AU - Carr, Darcy B.

AU - Kahn, Steven E.

AU - Hughes, James P.

AU - Rutledge, Elizabeth A.

AU - Van Yserloo, Brian

AU - Yukawa, Michi

AU - Weigle, David S.

PY - 2008/3

Y1 - 2008/3

N2 - Context: The expression of adipogenic genes in sc adipose tissue has been reported to be lower among patients with HIV-associated lipoatrophy than HIV-uninfected controls. It is unclear whether this is a result or cause of lipoatrophy. Objective: The objective of the study was to investigate the temporal relationships among changes in adipogenic gene expression in sc adipose tissue and changes in body fat distribution and metabolic complications in HIV-infected subjects on antiretroviral therapy. Design: This was a prospective longitudinal study. Setting: The study was conducted at HIV clinics in Seattle, Washington. Participants: The study population included 31 HIV-infected and 12 control subjects. Interventions: Subjects were followed up for 12 months after they initiated or modified their existing antiretroviral regimen. Main Outcome Measures: Changes in body composition, plasma lipids, insulin sensitivity, and gene expression in sc abdominal and thigh adipose tissue. Results: Subjects who developed lipoatrophy (n = 10) had elevated fasting triglycerides [3.16 (SD 2.79) mmol/liter] and reduced insulin sensitivity as measured by frequently sampled iv glucose tolerance test [1.89 (SD 1.27) × 10-4 min-1/μU·ml] after 12 months, whereas those without lipoatrophy (n = 21) did not show any metabolic complications [triglycerides 1.32 (SD 0.58) mmol/liter, P = 0.01 vs. lipoatrophy; insulin sensitivity 3.52 (SD 1.91) × 10-4 min-1/μU·ml, P = 0.01 vs. lipoatrophy]. In subjects developing lipoatrophy, the expression of genes involved in adipocyte differentiation, lipid uptake, and local cortisol production in thigh adipose tissue was significantly reduced already at the 2-month visit, several months before any loss of extremity fat mass was evident. Conclusions: In HIV-infected subjects, lipoatrophy is associated with elevated fasting triglycerides and insulin resistance and might be caused by a direct or indirect effect of antiretroviral drugs on sc adipocyte differentiation.

AB - Context: The expression of adipogenic genes in sc adipose tissue has been reported to be lower among patients with HIV-associated lipoatrophy than HIV-uninfected controls. It is unclear whether this is a result or cause of lipoatrophy. Objective: The objective of the study was to investigate the temporal relationships among changes in adipogenic gene expression in sc adipose tissue and changes in body fat distribution and metabolic complications in HIV-infected subjects on antiretroviral therapy. Design: This was a prospective longitudinal study. Setting: The study was conducted at HIV clinics in Seattle, Washington. Participants: The study population included 31 HIV-infected and 12 control subjects. Interventions: Subjects were followed up for 12 months after they initiated or modified their existing antiretroviral regimen. Main Outcome Measures: Changes in body composition, plasma lipids, insulin sensitivity, and gene expression in sc abdominal and thigh adipose tissue. Results: Subjects who developed lipoatrophy (n = 10) had elevated fasting triglycerides [3.16 (SD 2.79) mmol/liter] and reduced insulin sensitivity as measured by frequently sampled iv glucose tolerance test [1.89 (SD 1.27) × 10-4 min-1/μU·ml] after 12 months, whereas those without lipoatrophy (n = 21) did not show any metabolic complications [triglycerides 1.32 (SD 0.58) mmol/liter, P = 0.01 vs. lipoatrophy; insulin sensitivity 3.52 (SD 1.91) × 10-4 min-1/μU·ml, P = 0.01 vs. lipoatrophy]. In subjects developing lipoatrophy, the expression of genes involved in adipocyte differentiation, lipid uptake, and local cortisol production in thigh adipose tissue was significantly reduced already at the 2-month visit, several months before any loss of extremity fat mass was evident. Conclusions: In HIV-infected subjects, lipoatrophy is associated with elevated fasting triglycerides and insulin resistance and might be caused by a direct or indirect effect of antiretroviral drugs on sc adipocyte differentiation.

UR - http://www.scopus.com/inward/record.url?scp=40849147033&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40849147033&partnerID=8YFLogxK

U2 - 10.1210/jc.2007-0197

DO - 10.1210/jc.2007-0197

M3 - Article

C2 - 18089690

AN - SCOPUS:40849147033

VL - 93

SP - 959

EP - 966

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 3

ER -