Adipose tissue inflammation and liver fat in patients with highly active antiretroviral therapy-associated lipodystrophy

Sevastianova, Ksenia; Sutinen, Jussi; Kannisto, Katja; Hamsten, Anders; Ristola, Matti; Yki‐Järvinen, Hannele

doi:10.1152/ajpendo.90224.2008

Cited by 56 publications

(45 citation statements)

References 54 publications

(59 reference statements)

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“…Higher serum MIP-1a may reflect increased gene expression of this cytokine from adipose tissue depots, as previously reported in studies of both obese HIVuninfected individuals and nonobese HIV-infected individuals with ART-associated lipodystrophy, or other cellular sources including T cells and macrophages. 21,[30][31][32] Increased expression of MIP-1a in adipose tissue promotes immune cell infiltration and in situ inflammation, and there is some evidence that MIP-1a, along with MIP-1b and RANTES, can inhibit CCR5-tropic HIV-1 infection of CD4 + T cells, macrophages, and dendritic cells. [33][34][35] This raises the possibility that the higher serum levels of MIP-1a in obese individuals could affect HIV-1 entry or replication in peripheral CD4 + T cells, but current published data on the relationship between serum MIP-1a and HIV replication or the response to ART are conflicting.…”

Section: Koethe Et Almentioning

confidence: 99%

Circulating Interleukin-6, Soluble CD14, and Other Inflammation Biomarker Levels Differ Between Obese and Nonobese HIV-Infected Adults on Antiretroviral Therapy

Koethe

Dee

Bian

et al. 2013

AIDS Research and Human Retroviruses

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Obesity and chronic, treated HIV infection are both associated with persistent systemic inflammation and a similar constellation of metabolic and cardiovascular diseases, but the combined effects of excess adiposity and HIV on circulating proinflammatory cytokines and other biomarkers previously shown to predict disease risk is not well described. We measured inflammation biomarker levels in 158 predominantly virologically suppressed adults on long-term antiretroviral therapy (ART) with a range of body mass index (BMI) values from normal to morbidly obese. We assessed the relationship between BMI and each biomarker using multivariable linear regression adjusted for age, sex, race, CD4+ count, tobacco use, data source, protease inhibitor use, and routine nonsteroidal antiinflammatory drug (NSAID) or aspirin use. Among normal-weight (n = 48) and overweight participants (n = 41; BMI < 30 kg/m 2 ), incremental BMI increases were associated with significantly higher serum highly sensitive C-reactive protein (hsCRP; b = 2.47, p = 0.02) and tumor necrosis factor (TNF)-a receptor 1 levels (b = 1.53, p = 0.03), and significantly lower CD14 levels (b = 0.84, p = 0.01), but similar associations were not observed in the obese participants. Among the obese (n = 69; BMI ‡ 30 kg/m 2 ), however, higher serum levels of interleukin-6 (IL-6; b = 1.30, p = 0.02) and macrophage inflammatory protein-1a (b = 1.77, p < 0.01) were associated with higher BMI, a finding not observed among the nonobese. Among all participants, IL-6 and TNF-a receptor 1 levels were most closely associated with hsCRP ( p < 0.01). Further studies are needed to determine whether higher serum inflammation biomarker levels found in obese HIV-infected individuals on ART reflect an increased likelihood of adverse health outcomes, or if novel markers to estimate mortality and disease risk are needed in this population.

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Section: Koethe Et Almentioning

confidence: 99%

Circulating Interleukin-6, Soluble CD14, and Other Inflammation Biomarker Levels Differ Between Obese and Nonobese HIV-Infected Adults on Antiretroviral Therapy

Koethe

Dee

Bian

et al. 2013

AIDS Research and Human Retroviruses

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“…Macrophage abundance is often increased in adipose tissue of both obese and lipodystrophic subjects [14][15][16][17][18][19][20] . Infiltration with activated pro-inflammatory T lymphocyte subsets and mast cells and loss of immunomodulatory and anti-inflammatory T lymphocyte subtypes occur before macrophage infiltration in obesity and may contribute to macrophage infiltration and activation [21][22][23][24][25] .…”

mentioning

confidence: 99%

“…Indeed, macrophages in lipodystrophic HIV-infected subjects may be involved in adipose tissue wasting [19,26] . Macrophage infiltration and recruitment in HIV-related lipodystrophy are closely related to anti-retroviral drug treatment [19,20] . This occurs in a fat-depot specific pattern [26] .…”

mentioning

confidence: 99%

Aging and Regional Differences in Fat Cell Progenitors – A Mini-Review

et al. 2010

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Fat mass and fat tissue distribution change dramatically throughout life. In old age, fat becomes dysfunctional and is redistributed from subcutaneous to intra-abdominal visceral depots as well as other ectopic sites, including bone marrow, muscle and the liver. These changes are associated with increased risk of metabolic syndrome. Fat tissue is a nutrient storage, endocrine and immune organ that undergoes renewal throughout the lifespan. Preadipocytes, which account for 15–50% of cells in fat tissue, give rise to new fat cells. With aging, declines in preadipocyte proliferation and differentiation likely contribute to increased systemic exposure to lipotoxic free fatty acids. Age-related fat tissue inflammation is related to changes that occur in preadipocytes and macrophages in a fat depot-dependent manner. Fat tissue inflammation frequently leads to further reduction in adipogenesis with aging, more lipotoxicity and activation of cellular stress pathways that, in turn, exacerbate inflammatory responses of preadipocytes and immune cells, establishing self-perpetuating cycles that lead to systemic dysfunction. In this review, we will consider how inherent, age-related, depot-dependent alterations in preadipocyte function contribute to age-related fat tissue redistribution and metabolic dysfunction.

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“…A local infl ammation was generally observed, with macrophage infi ltration, increased expression of interleukin-6 (IL-6) and tumor necrosis factor-␣ (TNF-␣ ), together with decreased expression of the main adipogenic genes ( 2,13,25,(27)(28)(29)(30)(31)(32)(33). This was associated with an increased level of systemic proinfl ammatory cytokines, such as IL-6 and TNF-␣ ( 2,25,32,33 ), and of FFA ( 14,16 ). The relative roles of the different antiretroviral drugs in that setting are diffi cult to decipher as these patients are generally taking a combination of NRTIs and PIs.…”

mentioning

confidence: 99%

Glyceroneogenesis is inhibited through HIV protease inhibitor-induced inflammation in human subcutaneous but not visceral adipose tissue

Leroyer

Vatier

Kadiri

et al. 2011

Journal of Lipid Research

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Adipose tissue exerts two important functions involved in the regulation of lipid metabolism and insulin sensitivity: 1 ) storage of FFA as triglycerides (TG) into adipocytes and their disposal by lipolysis, and 2 ) secretion of adipokines and cytokines that could promote either insulin sensitivity or resistance in target tissues. Type 2 diabetes has been shown to be associated with disturbances in glucose and lipid metabolism, with modifi cations in systemic levels of adipokines, cytokines, and FFAs, partly as a consequence of adipose tissue dysfunction and infl ammation. In particular, dysregulation of FFA metabolism would be an essential cause of metabolic anomalies because a defect in their storage into adipocytes could lead to their ectopic depot in the liver, muscles, heart, and pancreas, where they play an important role in dyslipidemia, insulin resistance, and altered glucose tolerance ( 1 ). Recently, the antiretroviral drugs given to patients to control human immunodeficiency virus (HIV) infection were recognized as responsible for metabolic alterations and abnormal adipose tissue distribution, together with modifi cations in adipokines, cytokines, and FFAs, and with ectopic depots of lipids in nonfat tissues, arguing for mechanisms common to those reported in diabetes ( 2, 3 ).We recently highlighted, in human adipose tissue, the importance of the metabolic pathway, glyceroneogenesis (GNG), which is able to limit FFA release to blood under physiological fasting situations and which is a new target of thiazolidinedione action ( 4-6 ). FFA re-esterifi cation via GNG was fi rst described by Ballard et al. ( 7 )

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Adipose tissue inflammation and liver fat in patients with highly active antiretroviral therapy-associated lipodystrophy

Abstract: Sevastianova K, Sutinen J, Kannisto K, Hamsten A, Ristola M, Yki-Järvinen H. Adipose tissue inflammation and liver fat in patients with highly active antiretroviral therapy-associated lipodystrophy.

Cited by 56 publications

References 54 publications

Circulating Interleukin-6, Soluble CD14, and Other Inflammation Biomarker Levels Differ Between Obese and Nonobese HIV-Infected Adults on Antiretroviral Therapy

Circulating Interleukin-6, Soluble CD14, and Other Inflammation Biomarker Levels Differ Between Obese and Nonobese HIV-Infected Adults on Antiretroviral Therapy

Aging and Regional Differences in Fat Cell Progenitors – A Mini-Review

Glyceroneogenesis is inhibited through HIV protease inhibitor-induced inflammation in human subcutaneous but not visceral adipose tissue

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