Summary of Study ST004309

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002725. The data can be accessed directly via it's Project DOI: 10.21228/M8DV7W This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST004309
Study TitleMetabolic reprogramming by caloric restriction enhances acute-phase virologic control and reduces chronic inflammation in SIV-infected rhesus macaques
Study TypeNon-human primate study
Study SummaryNutrient metabolism influences HIV-1 replication, immunity, and chronic inflammation, yet is difficult to leverage for therapeutic gain. We sought to modulate metabolism in the non-human primate model of HIV-1 by caloric restriction (CR) without causing malnutrition, a modality canonically known for its anti-aging benefits. Four months of 30% CR was safe and resulted in broad metabolic reprogramming in healthy male and female rhesus macaques. Relative to that of ad libitum-fed animals, CR reduced acute phase viremia upon infection with SIV and notably enhanced the cycling of memory CD8⁺ T cells and NK cells in lymphoid tissues. During virologic suppression with antiretroviral therapy (ART), CR reduced the densities of activated lymphocytes in the GI tract and caused a systemic down-regulation of soluble inflammatory media-tors. Interrogating the plasma metabolome across infection revealed a contribution of distinct metabolic states to outcome, with glycolytic signatures associated with im-proved virologic control during acute SIV, and tricarboxylic acid cycle metabolites linked to an anti-inflammatory state during ART. These data highlight that manipulating metabolism through diet can enhance immunity and limit pathology in a primate lentiviral infection and reveal context-dependent metabolic programs associated with improved outcomes in SIV.
Institute
Tulane National Biomedical Research Center
DepartmentImmunology
Last NameNaveen
First NameSuresh Babu
Address18703 Three Rivers Road, Covington, Louisiana, USA, 70433.
Emailnsureshbabu@tulane.edu
Phone4126264523
Submit Date2025-10-17
Raw Data AvailableYes
Raw Data File Type(s)mzML, raw(Thermo)
Analysis Type DetailLC-MS
Release Date2025-11-14
Release Version1
Suresh Babu Naveen Suresh Babu Naveen
https://dx.doi.org/10.21228/M8DV7W
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR002725
Project DOI:doi: 10.21228/M8DV7W
Project Title:Plasma metabolomics study on calorie restriction in rhesus macaques
Project Summary:This project aimed to assess plasma metabolite concentrations using LC-MS in two cohorts of rhesus macaques. The ad-libitum (AL, n = 11) cohort consisted of animals fed without restriction, while the calorie-restricted (CR, n = 6) cohort received a diet restricted by up to 30% of their baseline intake. Plasma samples were collected at three time points: uninfected baseline (labeled in the study design as Ad-libitum and CR), 14 days post-SIV infection (labelled as Ad-libitum+SIV, CR+SIV), and 11 months post-ART (labelled as Ad-libitum+SIV+ART, CR+SIV+ART). LC-MS metabolomics was performed on all six CR animals at every time point. In the AL cohort, only six of the eleven animals were profiled due to the high cost of metabolomics; these same six animals were sampled at all time points to maintain consistency and enable statistical comparisons without confounding.
Institute:Tulane National Biomedical Research Center
Department:Immunology
Laboratory:Joseph Mudd
Last Name:Suresh Babu
First Name:Naveen
Address:18703 Three Rivers Road, Covington, Louisiana, USA, 70433.
Email:nsureshbabu@tulane.edu
Phone:4126264523

Subject:

Subject ID:SU004463
Subject Type:Mammal
Subject Species:Macaca mulatta
Taxonomy ID:9544

Factors:

Subject type: Mammal; Subject species: Macaca mulatta (Factor headings shown in green)

mb_sample_id local_sample_id Sample source Experimental_condition
SA505450A6_IF12Plasma Ad-Libitum
SA505451A2_KF18Plasma Ad-Libitum
SA505452A1_JH80Plasma Ad-Libitum
SA505453A5_JL54Plasma Ad-Libitum
SA505454A4_MF56Plasma Ad-Libitum
SA505455A3_JN26Plasma Ad-Libitum
SA505456B4_KF18Plasma Ad-Libitum + SIV
SA505457B8_IF12Plasma Ad-Libitum + SIV
SA505458B6_MF56Plasma Ad-Libitum + SIV
SA505459B5_JN26Plasma Ad-Libitum + SIV
SA505460B7_JL54Plasma Ad-Libitum + SIV
SA505461B3_JH80Plasma Ad-Libitum + SIV
SA505462B3_MF56_ARTPlasma Ad-libitum+SIV+ART
SA505463A4_HP61_ARTPlasma Ad-libitum+SIV+ART
SA505464A3_JL60_ARTPlasma Ad-libitum+SIV+ART
SA505465A2_IB41_ARTPlasma Ad-libitum+SIV+ART
SA505466A1_JD37_ARTPlasma Ad-libitum+SIV+ART
SA505467B2_KF18_ARTPlasma Ad-libitum+SIV+ART
SA505468A5_IF12_ARTPlasma Ad-libitum+SIV+ART
SA505469B4_JH80_ARTPlasma Ad-libitum+SIV+ART
SA505470B5_JN26_ARTPlasma Ad-libitum+SIV+ART
SA505471B1_JL54_ARTPlasma Ad-libitum+SIV+ART
SA505472B2_KD65Plasma CR
SA505473A7_KN43Plasma CR
SA505474A9_JL97Plasma CR
SA505475A10_JJ45Plasma CR
SA505476B1_JN33Plasma CR
SA505477A8_JT07Plasma CR
SA505478C3_JN33Plasma CR + SIV
SA505479C4_KD65Plasma CR + SIV
SA505480C2_JJ45Plasma CR + SIV
SA505481B10_JT07Plasma CR + SIV
SA505482B9_KN43Plasma CR + SIV
SA505483C1_JL97Plasma CR + SIV
SA505484C1_JL97_ARTPlasma CR+SIV+ART
SA505485C2_KN43_ARTPlasma CR+SIV+ART
SA505486C3_JT07_ARTPlasma CR+SIV+ART
SA505487C4_KD65_ARTPlasma CR+SIV+ART
SA505488C5_JN33_ARTPlasma CR+SIV+ART
SA505489D1_JJ45_ARTPlasma CR+SIV+ART
Showing results 1 to 40 of 40

Collection:

Collection ID:CO004456
Collection Summary:This study included adult, non-obese, male and female Indian-origin rhesus macaques divided into two age-, sex-, and weight-matched cohorts, namely ad-libitum/AL cohort (fed as needed) and calorie-restricted/CR cohort (food restricted to 70% of baseline feeding habit). Following caloric restriction in the CR cohort, both the AL and CR groups were intravenously (i.v.) infected with 5,000 IU/mL of genetically barcoded SIVmac239M virus. At 28 days post-infection, all animals, regardless of their experimental status, were started on combined antiretroviral therapy (cART) composed of a regimen of three antiretroviral drugs: TDF (Tenofovir disoproxil fumarate; ~5 mg/kg), FTC (Emtricitabine; ~38 mg/kg), and DTG (Dolutegravir; ~2.5 mg/kg). LC-MS metabolomics was performed on plasma samples isolated on day 14 post-infection and 11 months post-antiretroviral therapy. All blood for the study was collected using EDTA-containing S-Monovette® tubes (Sarstedt Inc., Newton, NC). Plasma isolation was carried out via centrifugation at 900 x g for 15 minutes. Following this, plasma was frozen down in 1 mL cryovials housed in Corning cool cells and stored for later usage at -80°C.
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR004472
Treatment Summary:Plasma samples were used without any treatment.

Sample Preparation:

Sampleprep ID:SP004469
Sampleprep Summary:Plasma samples from ad-libitum and caloric-restriction groups were simultaneously extracted. An established protocol was followed, wherein the samples were first added to a metabolite extraction plate containing a sorbent filter for protein precipitation & phospholipid removal, followed by the addition of 99% LC-MS grade acetonitrile with 1% formic acid to the plate, at a 3:1 acetonitrile-to-sample volume ratio. The solution containing the metabolites was pushed through the sorbent filter of the plate using a positive pressure-96 processor and collected in an MS plate, while the protein and phospholipids remained trapped in the sorbent filter of the plate. The metabolite solution was then dried to 150uL, ready for acquisition.

Chromatography:

Chromatography ID:CH005447
Instrument Name:Thermo Vanquish
Column Name:Discovery HSF5 column (15 cm × 2.1 mm, 3 um particle size)
Column Temperature:35° C
Flow Gradient:2% B from 0 to 1 minutes, then increase from 2% to 100% B from 1 to 5.5 minutes, then hold at 100% B from 5.5 to 7 minutes. At 7 minutes, decrease from 100% to 2%B. Hold at 2% B from 7 to 9 minutes.
Flow Rate:0.7mL/min
Solvent A:100% water; 0.1% formic acid
Solvent B:100% acetonitrile; 0.1% formic acid
Chromatography Type:Reversed phase

Analysis:

Analysis ID:AN007172
Analysis Type:MS
Chromatography ID:CH005447
Num Factors:6
Num Metabolites:236
Units:Normalized intensity
  
Analysis ID:AN007173
Analysis Type:MS
Chromatography ID:CH005447
Num Factors:6
Num Metabolites:215
Units:Normalized intensity
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