Short Communication: The Relationship Between Mitochondrial Dysfunction and Insulin Resistance in HIV-Infected Children Receiving Antiretroviral Therapy

Sharma, Tanvi; Jacobson, Denise L.; Anderson, Lisa; Gerschenson, Mariana; Dyke, Russell B. Van; McFarland, Elizabeth J.

doi:10.1089/aid.2012.0354

Cited by 17 publications

(16 citation statements)

References 25 publications

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“…Mitochondria produce energy from fatty acids or glucose via oxidative phosphorylation (OXPHOS). When OXPHOS is altered or dysfunctional, oxygen consumption is reduced and reactive oxygen species (ROS)/oxidative stress ensues leading to altered ATP/ADP ratios [10]. Clinically, direct inhibition of OXPHOS in muscle cells results in increased glucose uptake and lactate production, reduced glycogen synthesis and lipid and glucose oxidation, and unchanged lipid uptake [5].…”

Section: Introductionmentioning

confidence: 99%

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Insulin resistance in HIV-infected youth is associated with decreased mitochondrial respiration

Takemoto

Miller

Wang

et al. 2017

Aids

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Objective:To identify relationships between insulin resistance (IR) and mitochondrial respiration in perinatally HIV-infected youth.Design:Case–control study.Methods:Mitochondrial respiration was assessed in perinatally HIV-infected youth in Tanner stages 2–5, 25 youth with IR (IR+) and 50 without IR (IR−) who were enrolled in the Pediatric HIV/AIDS Cohort Study. IR was defined as a homeostatic model of assessment for IR value at least 4.0. A novel, high-throughput oximetry method was used to evaluate cellular respiration in peripheral blood mononuclear cells. Unadjusted and adjusted differences in mitochondrial respiration markers between IR+ and IR− were evaluated, as were correlations between mitochondrial respiration markers and biochemical measurements.Results:IR+ and IR− youth were similar on age, sex, and race/ethnicity. Mean age was 16.5 and 15.6 years in IR+ and IR−, respectively. The IR+ group had significantly higher mean BMI and metabolic analytes (fasting glucose, insulin, cholesterol, triglycerides, and venous lactate and pyruvate) compared with the IR−. Mitochondrial respiration markers were, on average, lower in the IR+ compared with IR−, including basal respiration (417.5 vs. 597.5 pmol, P = 0.074), ATP production (11 513 vs. 15 202 pmol, P = 0.078), proton leak (584.6 vs. 790.0 pmol, P = 0.033), maximal respiration (1815 vs. 2399 pmol, P = 0.025), and spare respiration capacity (1162 vs. 2017 pmol, P = 0.032). Nonmitochondrial respiration did not differ by IR status. The results did not change when adjusted for age.Conclusion:HIV-infected youth with IR have lower mitochondrial respiration markers when compared to youth without IR. Disordered mitochondrial respiration may be a potential mechanism for IR in this population.

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Section: Introductionmentioning

confidence: 99%

“…There are limited reports on the relationship of mitochondrial function and IR in HIV-infected youth [3,10]. Mitochondria play an integral role in cellular respiration, the biochemical processes that convert nutrients into usable energy (ATP) through the utilization of oxygen.…”

Section: Introductionmentioning

confidence: 99%

Insulin resistance in HIV-infected youth is associated with decreased mitochondrial respiration

Takemoto

Miller

Wang

et al. 2017

Aids

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“…Effective drug regimens are extending patient life into unchartered territories; chronic HIV infection and antiretroviral therapies (ART) have been documented to affect mitochondria function, insulin resistance and lipoatrophy (Montaner et al, 2003; Havlir and Currier, 2006; Sharma et al, 2013). Despite reduced peripheral viral load and lower rates of HIV-associated dementia (HAD), milder forms of HIV associated neurocognitive disorders (HAND) persist (Heaton et al, 2010; Heaton et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Alterations in the Levels of Vesicular Trafficking Proteins Involved in HIV Replication in the Brains and CSF of Patients with HIV-associated Neurocognitive Disorders

Fields

Dumaop

Adame

et al. 2013

J Neuroimmune Pharmacol

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Human immunodeficiency virus (HIV) associated neurocognitive disorders (HAND) remain prevalent despite improved antiretroviral therapies. A HAND-specific biomarker indicative of neuropsychological impairment (NPI) would give insight into disease progression and aid clinicians in designing therapy. Endosomal sorting complex required for transport (ESCRT) proteins such as tumor susceptibility gene (TSG)-101, vacuolar protein sorting (VPS)-4 and LIP-5 are important for HIV replication and recently antiviral interferon stimulated gene (ISG)-15 was proposed as a biomarker for CNS injury. Here, we analyzed a well-characterized cohort of HIV+ cerebral spinal fluid (CSF) and postmortem brain specimens for multiple vesicular trafficking proteins and a related innate immune protein, ISG-15, TSG-101, VPS-4 and LIP-5. All protein levels trended higher with increased NPI and neuropathology. ISG-15 CSF levels were increased in HIV encephalitis (HIVE) compared to normal cases, and three quarters of HIVE samples had above average CSF ISG-15 levels. VPS-4 CSF levels were increased in NPI/NPI-O compared to normal patients. VPS-4 CSF levels in HIV-associated dementia were equivalent to that of normal patients. LIP-5 CSF levels positively correlate with ISG-15 levels, and higher than average ISG-15 levels indicate elevated viral load. Immunoblot and immunohistochemical analyses show increased expression of ISG-15, VPS-4 and LIP-5 in neuronal cell bodies and astroglial cells. ESCRT protein CSF levels analyzed in conjunction with viral load may be indicative of NPI stage, and may aid in the diagnosis and design of therapies for HIV patients. Further studies on the ESCRT protein expression during HIV infection may lead to a promising biomarker for predicting progression of NPI.

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“…Currently, most of the literature focuses on the proportion of abnormal lipid metabolism in patients treated with ART. As reported in the literature, the incidence of dyslipidemia in HIV/AIDS patients is quite high in Asia, especially in some southeast Asian countries, such Thailand (34.93%) [19], Tanzania (more than 76%) [20], southern Ethiopia (82.3%) [21] and India (20-100%) [22][23][24][25]. It has also been reported that 10-60% of patients receiving ART treatment have hypercholesterolemia [8,[26][27][28][29], 20-70% have hypertriglyceridemia [8,9,29,30], 35.1% have hyper-low-density lipoprotein cholesterolemia [29], and 20-68.5% have hypo-highdensity lipoprotein cholesterolemia [9,[29][30][31][32].…”

Section: Discussionmentioning

confidence: 99%

Gradual increases in dyslipidemia among male patients with human immunodeficiency virus primarily treated with tenofovir plus lamivudine plus efavirenz: a 3-year follow-up study

Liu¹,

Zhang²,

Kang³

et al. 2021

Preprint

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Introduction: Since the development of antiretroviral therapy (ART) with TDF plus 3TC plus EFV, this specific regimen has not been studied enough with long-term lipid and uric monitoring.Methods: A prospective follow-up cohort study was performed. Sixty-one treatment-naive male patients with HIV were divided into three groups based on their baseline CD4+ T cell count (26, 12, and 23 patients in the <200, 200 to 350, and >350 groups, respectively). The lipid and purine metabolism parameters of the patients over 144 weeks were analyzed.Result: TG, TC, LDL-c and HDL-c levels all gradually increased over 144 weeks, but the increases in TC levels and HDL-c levels were significant (P=0.001, 0.000, respectively). Moreover, the percentages of hypercholesterolemia, hyper LDL cholesterolemia and hypertriglyceridemia all showed gradual and nonsignificant increases; the percentage of low HDL cholesterolemia showed a gradual and significant decrease (P=0.0007). Furthermore, the lower the baseline CD4+ T lymphocyte counts were, the higher the TG levels were and the lower the TC, LDL-c and HDL-c levels were. However, only baseline LDL-c levels differed significantly between the three groups (P=0.0457). Although the UA level and the percentages of hyperuricemia gradually increased over 144 weeks, there was no significant difference between the different follow-up time point groups or between the three CD4+ T cell count groups (all P>0.05). Further analyses revealed that the main factors contributing to lipid metabolism were age, anthropometric parameters and follow-up weeks, and virus load was the main factor contributing to uric acid levels.Conclusions: These findings provide a reference for clinicians to monitor lipid metabolism parameters closely during long-term ART with the TDF plus 3TC plus EFV regimen.

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Short Communication: The Relationship Between Mitochondrial Dysfunction and Insulin Resistance in HIV-Infected Children Receiving Antiretroviral Therapy

Cited by 17 publications

References 25 publications

Insulin resistance in HIV-infected youth is associated with decreased mitochondrial respiration

Insulin resistance in HIV-infected youth is associated with decreased mitochondrial respiration

Alterations in the Levels of Vesicular Trafficking Proteins Involved in HIV Replication in the Brains and CSF of Patients with HIV-associated Neurocognitive Disorders

Gradual increases in dyslipidemia among male patients with human immunodeficiency virus primarily treated with tenofovir plus lamivudine plus efavirenz: a 3-year follow-up study

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