Recombinant methionyl human leptin therapy in replacement doses improves insulin resistance and metabolic profile in patients with lipoatrophy and metabolic syndrome induced by the highly active antiretroviral therapy.

Lee, Jennifer H.; Chan, Jean L.; Sourlas, Epaminondas; Raptopoulos, Vassilios; Mantzoros, Christos S.

doi:10.1210/jc.2005-1545

Cited by 163HIV-related health complications and treatmentsAdipokines, Inflammation, and Metabolic DiseasesRegulation of Appetite and Obesity

Recombinant methionyl human leptin therapy in replacement doses improves insulin resistance and metabolic profile in patients with lipoatrophy and metabolic syndrome induced by the highly active antiretroviral therapy.

Lee, Jennifer H., Chan, Jean L., Sourlas, Epaminondas, Raptopoulos, Vassilios, Mantzoros, Christos S.·2006·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2005-1545

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Abstract

CONTEXT: Highly active antiretroviral therapy (HAART) for HIV-1 infection has been associated with a metabolic syndrome characterized by insulin resistance, hyperlipidemia, and redistribution of body fat (lipodystrophy). A subset of patients with predominant lipoatrophy has low levels of the adipocyte-secreted hormone leptin. OBJECTIVE: The objective of the study was to assess whether administration of recombinant methionyl human leptin (r-metHuLeptin) improves insulin resistance and other metabolic abnormalities in HIV+ leptin-deficient subjects with HAART-induced lipoatrophy. DESIGN, SETTING, PATIENTS, AND INTERVENTION: We conducted a randomized, placebo-controlled, double-blinded, crossover study from 2002 to 2004 in seven HIV+ men with HAART-induced lipoatrophy, serum leptin level less than 3 ng/ml, and fasting triglyceride level greater than 300 mg/dl, who were administered placebo for 2 months before or after administration of r-metHuLeptin at physiological doses for an additional 2 months. MAIN OUTCOME MEASURES: Insulin resistance, lipid levels, inflammatory markers, body composition, and HIV control were measured. RESULTS: Compared with placebo, r-metHuLeptin therapy improved fasting insulin levels, insulin resistance (as expressed by the homeostasis model assessment index and an insulin suppression test), and high-density lipoprotein. Body weight and fat mass decreased on r-metHuLeptin, mainly due to a decrease in truncal fat but not peripheral fat or lean body mass. r-metHuLeptin was well tolerated, and HIV control was not adversely affected. CONCLUSIONS: r-metHuLeptin replacement at physiological doses in HIV+ leptin-deficient patients with HAART-induced lipoatrophy improves insulin resistance, high-density lipoprotein, and truncal fat mass. Future larger and more long-term studies in HAART-induced lipoatrophy, including patients with more severe metabolic abnormalities, are warranted to evaluate the physiological and potentially therapeutic role of r-metHuLeptin for this condition and to fully clarify the underlying mechanisms of action.

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Leptin concentrations are positively correlated with the amount of body fat.
“Leptin concentrations are positively correlated with the amount of body fat (4-10).”
From Leptin in humans: lessons from translational research (2009) · cites this paper as [10]
Leptin administration in replacement doses significantly improved glycemia, dyslipidemia, and hepatic steatosis in lipoatrophic, hypoleptinemic patients with severe insulin resistance.
“It has been shown that leptin administration in replacement doses significantly improved glycemia, dyslipidemia, and hepatic steatosis in lipoatrophic, hypoleptinemic patients with severe insulin resistance.”
From Leptin in humans: lessons from translational research (2009) · cites this paper as [10]
Leptin administration improved lipidemia and insulin resistance in HIV-positive patients with partial lipoatrophy.
“It also improved lipidemia and insulin resistance in HIVpositive patients with partial lipoatrophy (10,(22)(23)(24)(25)(26).”
From Leptin in humans: lessons from translational research (2009) · cites this paper as [10]
r-metHuLeptin therapy in replacement doses improved insulin resistance and metabolic profile in patients with lipoatrophy and metabolic syndrome induced by highly active antiretroviral therapy.
“r-metHuLeptin therapy in replacement doses improved insulin resistance and metabolic profile in patients with lipoatrophy and metabolic syndrome induced by the highly active antiretroviral therapy (10).”
From Leptin in humans: lessons from translational research (2009) · cites this paper as [10]
The finding of body fat loss with metreleptin has also been observed in studies assessing metreleptin in humans with severe lipodystrophy and other conditions associated with relative leptin deficiency.
“This fi nding also has been observed in studies assessing the effect of metreleptin on metabolic parameters in humans with severe lipodystrophy and other conditions associated with relative leptin de fi ciency (39 -41).”
From Leptin is an effective treatment for hypothalamic amenorrhea (2011) · cites this paper as [40]

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Authors: Lee, J. H., Chan, J. L., Sourlas, E., Raptopoulos, V., & Mantzoros, C. S.
Affiliations: Division of Endocrinology, Diabetes, and Metabolism (J.H.L., J.L.C., C.S.M.) Boston, Massachusetts 02215
Boston University (US)
Beth Israel Deaconess Medical Center (US)
Corresponding author: Mantzoros, Christos S.
ORCID: Lee, Jennifer H.
Mantzoros, Christos S.
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2006-07-01
Volume: 91
Issue: 7
Pages: 2605-2611
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2005-1545
OpenAlex: W2118921194
Cited by: 163
References: 48
Citations by year: 2024: 4 · 2023: 5 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 7 · 2016: 7 · 2015: 8 · 2014: 20 · 2013: 12 · 2012: 12
FWCI: 15.70
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Public Health Service (R0-158785)
National Institute of Diabetes and Digestive and Kidney Diseases (5T32-DK-07516-18, T32DK007516)
National Center for Research Resources (M01RR001032, K23RR018860)
Topics: Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords: leptin replacement therapy, metabolic syndrome, insulin resistance, HIV infection, leptin deficiency, hypertriglyceridemia, HDL cholesterol, truncal fat, body composition, HIV viral load
MeSH terms: Acquired Immunodeficiency Syndrome, Adolescent, Adult, Body Composition, Double-Blind Method, Humans, Insulin, Insulin Resistance, Lipids, Lipoproteins, HDL, Male, Placebos, Recombinant Proteins, HIV-1, Interleukin-6, Body Mass Index, Cross-Over Studies, Leptin, Antiretroviral Therapy, Highly Active, Metabolic Syndrome, HIV-Associated Lipodystrophy Syndrome

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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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Recombinant methionyl human leptin therapy in replacement doses improves insulin resistance and metabolic profile in patients with lipoatrophy and metabolic syndrome induced by the highly active antiretroviral therapy.

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