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Altered fat differentiation and adipocytokine expression are inter-related and linked to morphological changes and insulin resistance in HIV-1-infected lipodystrophic patients.
Antivir Ther 2004; 9(4):555-64AT

Abstract

OBJECTIVE

To achieve a better understand of the pathophysiology of HIV-related lipoatrophy, we compared the mRNA expression of adipocytokines in fat samples from patients and healthy HIV-seronegative controls together with fat morphology and we studied the relationship between changes in fat morphology, adipocytokine expression, markers of adipose tissue differentiation and whole body insulin sensitivity.

DESIGN

Cross-sectional analytical study.

SUBJECTS AND METHODS

The mRNA expression of adipocytokines and transcriptional factors in fat samples from 26 patients with peripheral lipoatrophy (all under anti-retroviral therapy associating protease inhibitor and nucleoside-analogue reverse transcriptase inhibitors) and from 16 non-HIV-infected controls was measured by real time quantitative RT-PCR. Fat morphology was assessed histologically on a subgroup of 10 patients and six controls: collagen fibres by Sirius Red staining, apoptosis by the TUNEL technique, vessels by smooth muscle alpha-actin staining and macrophages by CD68 staining. Insulin resistance was assessed by using the homeostasis model assessment.

RESULTS

The patients' fat showed higher values of apoptosis (P=0.005), fibrosis (P<0.05), vessel density (P=0.001) and macrophage infiltration (P<0.05) than the controls' fat, together with lower adiponectin and leptin mRNA levels and higher interleukin (IL)-6 and tumour necrosis factor (TNF)alpha mRNA levels. TNFa and IL-6 expression correlated positively with the level of apoptosis (P=0.05 and P<0.05, respectively) and negatively with CCAAT-enhancer binding protein (C/EBP)alpha (P<0.001 and P<0.05, respectively). Apoptosis correlated negatively with the expression level of sterol-regulatory-element-binding-protein-1c (SREBP1c) (P=0.01) and C/EBPalpha (P=0.01) whilst the vessel density correlated negatively with SREBP1c (P<0.005), C/EBPalpha (P=0.001) and beta (P=0.001). Adiponectin and leptin expression correlated positively with each other, and also with adipogenic marker expression and overall insulin sensitivity. These relationships were also present when the patient group was studied separately. Finally, fat morphological abnormalities correlated positively with whole body insulin resistance.

CONCLUSIONS

Adipose tissue from patients with HIV-1-related lipoatrophy shows increased apoptosis, together with decreased adipocyte differentiation. Increased TNFalpha and IL-6 expression could be a major phenomenon linking these alterations. Decreased adiponectin and leptin expression, which may result from decreased adipocyte differentiation, could be involved in the observed whole body insulin resistance.

Authors+Show Affiliations

INSERM Research Unit 402, Faculty of Medicine Saint-Antoine, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15456087

Citation

Jan, Véronique, et al. "Altered Fat Differentiation and Adipocytokine Expression Are Inter-related and Linked to Morphological Changes and Insulin Resistance in HIV-1-infected Lipodystrophic Patients." Antiviral Therapy, vol. 9, no. 4, 2004, pp. 555-64.
Jan V, Cervera P, Maachi M, et al. Altered fat differentiation and adipocytokine expression are inter-related and linked to morphological changes and insulin resistance in HIV-1-infected lipodystrophic patients. Antivir Ther (Lond). 2004;9(4):555-64.
Jan, V., Cervera, P., Maachi, M., Baudrimont, M., Kim, M., Vidal, H., ... Bastard, J. P. (2004). Altered fat differentiation and adipocytokine expression are inter-related and linked to morphological changes and insulin resistance in HIV-1-infected lipodystrophic patients. Antiviral Therapy, 9(4), pp. 555-64.
Jan V, et al. Altered Fat Differentiation and Adipocytokine Expression Are Inter-related and Linked to Morphological Changes and Insulin Resistance in HIV-1-infected Lipodystrophic Patients. Antivir Ther (Lond). 2004;9(4):555-64. PubMed PMID: 15456087.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Altered fat differentiation and adipocytokine expression are inter-related and linked to morphological changes and insulin resistance in HIV-1-infected lipodystrophic patients. AU - Jan,Véronique, AU - Cervera,Pascale, AU - Maachi,Mustapha, AU - Baudrimont,Marielle, AU - Kim,Minji, AU - Vidal,Hubert, AU - Girard,Pierre-Marie, AU - Levan,Philippe, AU - Rozenbaum,Willy, AU - Lombès,Anne, AU - Capeau,Jacqueline, AU - Bastard,Jean-Philippe, PY - 2004/10/1/pubmed PY - 2005/4/7/medline PY - 2004/10/1/entrez SP - 555 EP - 64 JF - Antiviral therapy JO - Antivir. Ther. (Lond.) VL - 9 IS - 4 N2 - OBJECTIVE: To achieve a better understand of the pathophysiology of HIV-related lipoatrophy, we compared the mRNA expression of adipocytokines in fat samples from patients and healthy HIV-seronegative controls together with fat morphology and we studied the relationship between changes in fat morphology, adipocytokine expression, markers of adipose tissue differentiation and whole body insulin sensitivity. DESIGN: Cross-sectional analytical study. SUBJECTS AND METHODS: The mRNA expression of adipocytokines and transcriptional factors in fat samples from 26 patients with peripheral lipoatrophy (all under anti-retroviral therapy associating protease inhibitor and nucleoside-analogue reverse transcriptase inhibitors) and from 16 non-HIV-infected controls was measured by real time quantitative RT-PCR. Fat morphology was assessed histologically on a subgroup of 10 patients and six controls: collagen fibres by Sirius Red staining, apoptosis by the TUNEL technique, vessels by smooth muscle alpha-actin staining and macrophages by CD68 staining. Insulin resistance was assessed by using the homeostasis model assessment. RESULTS: The patients' fat showed higher values of apoptosis (P=0.005), fibrosis (P<0.05), vessel density (P=0.001) and macrophage infiltration (P<0.05) than the controls' fat, together with lower adiponectin and leptin mRNA levels and higher interleukin (IL)-6 and tumour necrosis factor (TNF)alpha mRNA levels. TNFa and IL-6 expression correlated positively with the level of apoptosis (P=0.05 and P<0.05, respectively) and negatively with CCAAT-enhancer binding protein (C/EBP)alpha (P<0.001 and P<0.05, respectively). Apoptosis correlated negatively with the expression level of sterol-regulatory-element-binding-protein-1c (SREBP1c) (P=0.01) and C/EBPalpha (P=0.01) whilst the vessel density correlated negatively with SREBP1c (P<0.005), C/EBPalpha (P=0.001) and beta (P=0.001). Adiponectin and leptin expression correlated positively with each other, and also with adipogenic marker expression and overall insulin sensitivity. These relationships were also present when the patient group was studied separately. Finally, fat morphological abnormalities correlated positively with whole body insulin resistance. CONCLUSIONS: Adipose tissue from patients with HIV-1-related lipoatrophy shows increased apoptosis, together with decreased adipocyte differentiation. Increased TNFalpha and IL-6 expression could be a major phenomenon linking these alterations. Decreased adiponectin and leptin expression, which may result from decreased adipocyte differentiation, could be involved in the observed whole body insulin resistance. SN - 1359-6535 UR - https://www.unboundmedicine.com/medline/citation/15456087/Altered_fat_differentiation_and_adipocytokine_expression_are_inter_related_and_linked_to_morphological_changes_and_insulin_resistance_in_HIV_1_infected_lipodystrophic_patients_ L2 - http://www.diseaseinfosearch.org/result/9735 DB - PRIME DP - Unbound Medicine ER -