Comparison of the influence of four classes of HIV antiretrovirals on adipogenic differentiation: the minimal effect of raltegravir and atazanavir

Minami, Ryoji; Yamamoto, Masahiro; Takahama, Soichiro; Ando, Hitoshi; Miyamura, Tomoya; Suematsu, Eiichi

doi:10.1007/s10156-010-0101-5

Cited by 36 publications

(25 citation statements)

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“…Furthermore, the ZAG protein may also be synthesized and secreted by mature adipocytes, with a close regulatory link with some adipokines and transcription factors such as peroxisome proliferator activated receptor gamma (PPARg) [9,10,[25][26][27]. Increased lipolysis may be a deleterious effect of many antiretroviral drugs from various drug families [28,29]. In our study, no relationship was found between ZAG levels and the family of antiretroviral drugs used.…”

Section: Discussioncontrasting

confidence: 45%

Zinc alpha‐2 glycoprotein is implicated in dyslipidaemia in HIV‐1‐infected patients treated with antiretroviral drugs

et al. 2012

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ObjectivesTreated HIV-1-infected patients with lipodystrophy often develop insulin resistance and proatherogenic dyslipidaemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized adipokine which has been shown to be involved in the development of obesity and metabolic syndrome in uninfected subjects. We assessed the relationship between circulating ZAG levels and metabolic derangements in HIV-1-infected patients receiving antiretroviral drugs. MethodsPlasma ZAG levels were assessed in 222 individuals: 166 HIV-1-infected patients treated with antiretroviral drugs (77 with lipodystrophy and 89 without lipodystrophy) and 56 uninfected controls. Plasma ZAG levels were assessed by enzyme-linked immunosorbent assay (ELISA) and were correlated with fat distribution abnormalities and metabolic parameters. ResultsHIV-1-infected patients had lower plasma ZAG levels compared with uninfected controls (P < 0.001). No differences were found in ZAG plasma levels according to the presence of lipodystrophy, components of the metabolic syndrome or type of antiretroviral treatment regimen. Circulating ZAG levels were strongly determined by high-density lipoprotein cholesterol (HDLc) in men (B = 0.644; P < 0.001) and showed a positive correlation with total cholesterol (r = 0.312; P < 0.001) and HDLc (r = 0.216; P = 0.005). ConclusionsHIV-1-infected patients have lower plasma ZAG levels than uninfected controls. In infected patients, plasma ZAG levels are in close relationship with total cholesterol and HDLc.Keywords: antiretroviral drugs, dyslipidaemia, HIV, lipodystrophy, metabolic syndrome, zinc alpha-2 glycoprotein Accepted 21 October 2011 IntroductionProlonged use of antiretroviral drugs in HIV-1-infected patients is associated with several toxicities that limit their success. Among chronic toxicities, the appearance of the so-called lipodystrophy syndrome is of concern. Lipodystrophy includes a series of body morphological changes consisting of peripheral fat atrophy, truncal fat accumulation or both [1]. Lipodystrophy is not a merely aesthetic abnormality; unfortunately it is often Adipose tissue, in addition to its well-known role in lipid storage, is an important secretory organ. Adipokine deregulation is known to be involved in the aetiology of IR and metabolic syndrome (MS) in uninfected subjects, but the relationship between adipokines, lipodystrophy and its metabolic complications is a subject of controversy [4][5][6]. Recently, abnormalities in circulating levels of several adipokines, such as leptin and adiponectin, have been described in individuals with HIV-1-related lipodystrophy [7]. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized adipokine that is a focus of special interest. This protein appears to be involved in lipid metabolism and body weight regulation and it may also be involved in the development of IR. In contrast to other adipokines, ZAG gene expression, similarly to expression of the adiponectin gene, is reduced in obesity [8][9][10]. However, it is unclear whether circulating leve...

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Section: Discussioncontrasting

confidence: 45%

Zinc alpha‐2 glycoprotein is implicated in dyslipidaemia in HIV‐1‐infected patients treated with antiretroviral drugs

et al. 2012

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“…11 However, a certain degree of mitochondrial toxicity is still present and will probably still affect HIV patients under ART, although to a lesser extent. [12][13][14] In fact, switch studies from d4T to other NRTIs and complete switch off of thymidine analogs showed modest even if consistent increases in limb fat. [15][16][17] The pathogenesis of lipohypertrophy appears to be multifactorial, with age, sex, HIV itself, immune depression, and duration and type of ART related to its appearance.…”

Section: Introductionmentioning

confidence: 97%

Polymorphisms inFasGene Is Associated with HIV-Related Lipoatrophy in Thai Patients

Likanonsakul

Rattanatham

Feangvad

et al. 2013

AIDS Research and Human Retroviruses

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The present study aimed to evaluate the role of genetic polymorphisms in the emergence of lipoatrophy or lipodystrophy in HIV-infected patients with antiretroviral therapy (ART) in Thailand. Position 455 upstream of the Apolipoprotein C3 gene (ApoC3 T-455C, rs2854116), codon 64 of the Beta3 adrenergic receptor gene (ARb3 Tcod64C, rs4994), and position 670 upstream of the Fas gene (Fas A-670G, rs1800682) were genotyped in 829 HIV-infected Thai patients who had started ART. Crude and adjusted incidence rate ratios (IRR) were calculated using Poisson regression. The serum levels of cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were also analyzed. Multivariate analysis revealed an association between the Fas -670AA genotype, but not the ApoC3 -455 or ARb3 cod64 genotypes, with the incidence of lipoatrophy after adjusting for gender and stavudine (d4T)-containing regimens (IRR = 1.72, 95% CI = 1.20-2.45, p = 0.003). However, ApoC3 -455C homozygous patients showed elevated serum levels of triglycerides, while this genotype did not affect serum total cholesterol, HDL, or LDL levels in patients with lipoatrophy or lipodystrophy. In contrast, the ARb3 cod64 genotype did not show any significant association with the serum levels of cholesterol, triglycerides, HDL, or LDL. In conclusion, Fas -670AA affected the incidence of lipoatrophy in HIV-1-infected Thai patients, while the ApoC3 -455C allele affected the serum levels of triglycerides. These results confirmed the role of genetics in the development of ART-related metabolic disorders.

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“…Stavudine (d4T), efavirenz (EFV), atazanavir (ATV), ritonavir (RTV) were obtained from NIH AIDS Research & Reference Reagent Program and used at clinically relevant concentrations (10 and 50 M), as well as ATV-boosted RTV (7.4 M ATV + 1.3 M RTV) [12].…”

Section: Reagents and Drugsmentioning

confidence: 99%

“…Similarly, NRTIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs) can modify adipocyte functions by modulating gene expression and increasing oxidative stress [6,7,11]. However, most mechanisms linking HAART to LD likely involve dysregulation of adipose cell growth and differentiation by both PIs and NRTIs, but studies are still far from being conclusive [12,13].…”

Section: Introductionmentioning

confidence: 99%

Different origin of adipogenic stem cells influences the response to antiretroviral drugs

Gibellini

Biasi

Nasi

et al. 2015

Experimental Cell Research

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Comparison of the influence of four classes of HIV antiretrovirals on adipogenic differentiation: the minimal effect of raltegravir and atazanavir

Cited by 36 publications

References 22 publications

Zinc alpha‐2 glycoprotein is implicated in dyslipidaemia in HIV‐1‐infected patients treated with antiretroviral drugs

Zinc alpha‐2 glycoprotein is implicated in dyslipidaemia in HIV‐1‐infected patients treated with antiretroviral drugs

Polymorphisms inFasGene Is Associated with HIV-Related Lipoatrophy in Thai Patients

Different origin of adipogenic stem cells influences the response to antiretroviral drugs

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