Leptin and Adiponectin in the HIV Associated Metabolic Syndrome: Physiologic and Therapeutic Implications

Tsiodras, Sotirios; Mantzoros, Christos S.

doi:10.3844/ajidsp.2006.141.152

Cited by 43 publications

(34 citation statements)

References 148 publications

(160 reference statements)

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“…35 Adipokines are dysregulated in HIV-infected persons. [36][37][38] Lean HIV-positive, ART-treated men had adiponectin levels similar to obese, insulin-resistant HIV-negative men, and those with extremity fat loss had even lower levels. 36 Baseline trunk and limb fat by DEXA did not differ by m.10398 allele in our analyses (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA Variation and Changes in Adiponectin and Endothelial Function in HIV-Infected Adults After Antiretroviral Therapy Initiation

Hulgan

Stein

Cotter

et al. 2013

AIDS Research and Human Retroviruses

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Studies in persons of European descent have suggested that mitochondrial DNA (mtDNA) haplogroups influence antiretroviral therapy (ART) toxicity. We explored associations between mtDNA variants and changes in endothelial function and biomarkers among non-Hispanic white, ART-naive subjects starting ART. A5152s was a substudy of A5142, a randomized trial of initial class-sparing ART regimens that included efavirenz or lopinavir/ritonavir with nucleoside reverse transcriptase inhibitors (NRTIs), or both without NRTIs. Brachial artery flow-mediated dilation (FMD) and cardiovascular biomarker assessments were performed at baseline and at weeks 4 and 24. Ten haplogroup-defining mtDNA polymorphisms were determined. FMD and biomarker changes from baseline to week 24 by mtDNA variant were assessed using Wilcoxon rank-sum tests. Thirty-nine non-Hispanic white participants had DNA and 24-week data. The nonsynonymous m.10398A > G mtDNA polymorphism (N = 8) was associated with higher median baseline adiponectin (5.0 vs. 4.2 lg/ml; p = 0.003), greater absolute ( -1.9 vs. -0.2 lg/ml) and relative ( -33% vs. -3%) adiponectin decreases ( p < 0.001 for both), and lower week 24 brachial artery FMD (3.6% vs. 5.4%; p = 0.04). Individual mtDNA haplogroups, including haplogroups H (N = 13) and U (N = 6), were not associated with adiponectin or FMD changes. In this small pilot study, adiponectin and brachial artery FMD on ART differed in non-Hispanic whites with a nonsynonymous mtDNA variant associated with several human diseases. These preliminary findings support the hypothesis that mtDNA variation influences metabolic ART effects. Validation studies in larger populations and in different racial/ethnic groups that include m.10398G carriers are needed.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA Variation and Changes in Adiponectin and Endothelial Function in HIV-Infected Adults After Antiretroviral Therapy Initiation

Hulgan

Stein

Cotter

et al. 2013

AIDS Research and Human Retroviruses

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“…HIV-associated lipoatrophy is a much more prevalent condition, affecting an estimated 15-36% of HIV-infected patients (120) and is closely linked with insulin resistance and dysregulation of peripheral adipose tissue metabolism (159,235,262). In our initial randomized, placebo-controlled, interventional study, we found that leptin in physiological doses improves insulin resistance, hyperlipidemia, and truncal fat mass in these patients (23,141).…”

Section: Lipodystrophymentioning

confidence: 93%

Leptin in human physiology and pathophysiology

Mantzoros

Magkos

Brinkoetter

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

509

322

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Leptin, discovered through positional cloning 15 years ago, is an adipocyte-secreted hormone with pleiotropic effects in the physiology and pathophysiology of energy homeostasis, endocrinology, and metabolism. Studies in vitro and in animal models highlight the potential for leptin to regulate a number of physiological functions. Available evidence from human studies indicates that leptin has a mainly permissive role, with leptin administration being effective in states of leptin deficiency, less effective in states of leptin adequacy, and largely ineffective in states of leptin excess. Results from interventional studies in humans demonstrate that leptin administration in subjects with congenital complete leptin deficiency or subjects with partial leptin deficiency (subjects with lipoatrophy, congenital or related to HIV infection, and women with hypothalamic amenorrhea) reverses the energy homeostasis and neuroendocrine and metabolic abnormalities associated with these conditions. More specifically, in women with hypothalamic amenorrhea, leptin helps restore abnormalities in hypothalamic-pituitary-peripheral axes including the gonadal, thyroid, growth hormone, and to a lesser extent adrenal axes. Furthermore, leptin results in resumption of menses in the majority of these subjects and, in the long term, may increase bone mineral content and density, especially at the lumbar spine. In patients with congenital or HIVrelated lipoatrophy, leptin treatment is also associated with improvements in insulin sensitivity and lipid profile, concomitant with reduced visceral and ectopic fat deposition. In contrast, leptin's effects are largely absent in the obese hyperleptinemic state, probably due to leptin resistance or tolerance. Hence, another emerging area of research pertains to the discovery and/or usefulness of leptin sensitizers. Results from ongoing studies are expected to further increase our understanding of the role of leptin and the potential clinical applications of leptin or its analogs in human therapeutics. adipokines; adipose tissue; leptin resistance; leptin deficiency; hypoleptinemia STUDIES OF GENETICALLY OBESE MICE serendipitously found in the Jackson Laboratories revealed that their phenotypes derive from homozygous mutations of either the obese (ob) or diabetic (db) genes that result in obesity and insulin resistance or diabetes as well as endocrine and immune dysfunction (53, 54,115,117,183,261). The gene mutation in the ob/ob mouse results in a complete deficiency of or a truncated and biologically inactive ob gene product (287); the latter subsequently was given the name leptin (95), from the Greek word "leptos" (meaning "thin"), because when this protein was given to the obese ob/ob mice they lost significant amounts of body weight. It was then recognized that the db gene codes for the leptin receptor (140). Consequently, exogenously administered leptin reduces body weight and resolves the metabolic, endocrine, and immune disturbances in ob/ob mice but has no effects in db/db mice (100, 111, 28...

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“…Leptin and adiponectin have both been implicated in combined antiretroviral therapy (cART)-related lipodystrophy and metabolic syndrome. 22,23 Leptin deficiency is associated with lipoatrophy, while low levels of adiponectin are associated with central fat accumulation and insulin resistance. 22 In addition to affecting metabolic pathways that lead to changes in fat distribution, leptin, and adiponectin also influence immune pathways that may both modulate HIV disease and influence BM responsiveness.…”

Section: Introductionmentioning

confidence: 99%

A polymorphism in the leptin gene promoter is associated with anemia in patients with HIV disease

Vanasse

Jeong

Tate

et al. 2011

Blood

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To study factors associated with anemia and its effect on survival in HIV-infected persons treated with modern combined antiretroviral therapy (cART), we characterized the prevalence of anemia in the Veterans Aging Cohort Study (VACS) and used a candidate gene approach to identify proinflammatory gene single nucleotide polymorphisms (SNPs) associated with anemia in HIV disease. The study comprised 1597 HIV ؉ and 865 HIV ؊ VACS subjects with DNA, blood, and annotated clinical data available for analysis. Anemia was defined according to World Health Organization criteria (hemoglobin < 13 g/dL and < 12 g/dL in men and women, respectively). The prevalence of anemia in HIV ؉ and HIV ؊ subjects was 23.1% and 12.9%, respectively. Independent of HIV status, anemia was present in 23.4% and 8% in blacks and whites, respectively. Analysis of our candidate genes revealed that the leptin ؊2548 G/A SNP was associated with anemia in HIV ؉ , but not HIV ؊ , patients, with the AA and AG genotypes significantly predicting anemia (P < .003 and P < .039, respectively, logistic regression). This association was replicated in an independent cohort of HIV ؉ women. Our study provides novel insight into the association between genetic variability in the leptin gene and anemia in HIV ؉ individuals.

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Leptin and Adiponectin in the HIV Associated Metabolic Syndrome: Physiologic and Therapeutic Implications

Cited by 43 publications

References 148 publications

Mitochondrial DNA Variation and Changes in Adiponectin and Endothelial Function in HIV-Infected Adults After Antiretroviral Therapy Initiation

Mitochondrial DNA Variation and Changes in Adiponectin and Endothelial Function in HIV-Infected Adults After Antiretroviral Therapy Initiation

Leptin in human physiology and pathophysiology

A polymorphism in the leptin gene promoter is associated with anemia in patients with HIV disease

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