Comprehensive metabolomics profiling reveals common metabolic alterations underlying the four major non-communicable diseases in treated HIV infection

Abstract

Background HIV infection and normal aging share immune and inflammatory changes that result in premature aging and non-communicable diseases (NCDs), but the exact pathophysiology is not yet uncovered. We identified the common metabolic pathways underlying various NCDs in treated HIV infection. Methods We performed untargeted metabolomics including 87 HIV-negative (–) normal controls (NCs), 87 HIV-positive (+) NCs, and 148 HIV+ subjects with only one type of NCDs, namely, subclinical carotid atherosclerosis, neurocognitive impairment (NCI), liver fibrosis (LF) and renal impairment. All HIV+ subjects were virally suppressed. Results HIV+ patients presented widespread alterations in cellular metabolism compared to HIV– NCs. Glycerophospholipid (GPL) metabolism was the only one disturbed pathway presented in comparisons including HIV– NCs across age groups, HIV+ NCs across age groups, HIV+ NCs vs HIV– NCs and each of HIV+ NCDs vs HIV+ NCs. D-glutamine and D-glutamate metabolism and alanine-aspartate-glutamate metabolism were presented in comparisons between HIV+ NCs vs HIV– NCs, HIV+ LF or HIV+ NCI vs HIV+ NCs. Consistently, subsequent analysis identified a metabolomic fingerprint specific for HIV+ NCDs, containing 42 metabolites whose relative abundance showed either an upward (mainly GPL-derived lipid mediators) or a downward trend (mainly plasmalogen phosphatidylcholines, plasmalogen phosphatidylethanolamines, and glutamine) from HIV– NCs to HIV+ NCs and then HIV+ NCDs, reflecting a trend of increased oxidative stress. Interpretation GPL metabolism emerges as the common metabolic disturbance linking HIV to NCDs, followed by glutamine and glutamate metabolism. Together, our data point to the aforementioned metabolisms and related metabolites as potential key targets in studying pathophysiology of NCDs in HIV infection and developing therapeutic interventions. Funding China National Science and Technology Major Projects on Infectious Diseases, National Natural Science Foundation of China, Yi-wu Institute of Fudan University, and Shanghai Municipal Health and Family Planning Commission.

Research Progress in the Epidemiology of HIV/AIDS in China

“…Very recently, Ding et al conducted a case-control study using untargeted metabolomics to characterize the key metabolites and metabolic pathways associated with HIV infection and multiple NCDs, focusing on identifying the common metabolic pathways underlying them ( 64 ). They found that PLWH presented widespread alterations in cellular metabolism versus HIV-negative individuals, and glycerophospholipid metabolism emerged as the potential common metabolic pathway underlying NCDs in treated HIV infection; followed by d-glutamine and d-glutamate, and alanine, aspartate and glutamate metabolism.…”

Metabolite variations in the sera of HIV+ patients after an oral administration of effervescent glutamine and in comparison to non-HIV individuals by NMR

“…HIV infection alters human cellular metabolism in many ways, favoring anabolic pathways, such as biosynthesis of nucleotides, phospholipids, cholesterol, amino acids, proteins, and glycoproteins, among others that are used for the assembly of newly synthesized viral particles. [1][2][3][4] Therefore, lipid, protein, and carbohydrate metabolism are expected to change greatly. 1 Additionally, antiretroviral therapy (ART) influences human metabolism by provoking side effects including metabolic syndrome which is characterized by increased abdominal fat, insulin resistance, type 2 diabetes, increased blood levels of free fatty acids, increased low-density lipoproteins (LDL), and verylow-density lipoproteins (VLDL), and, not rarely, premature aging.…”

“…4 It is also common to expect modified levels of glutamine, glutamate, and alanine-aspartateglutamate in HIV+ individuals. 7 Interesting metabolomic research on HIV/AIDS serum, and plasma, applying targeted or untargeted approaches 3,[7][8][9][10][11] had been published, with revealed changes in lipids, glucose, amino acids, choline, proteins, valine, and glutamine levels. 12 Glutamine plays many important metabolic roles, as a precursor of glutathione, purines, and glutamate.…”

Utilizing Go-Yoga Smartphone Application to Prevent Preeclampsia in Pregnant Women

“…In addition to being related to maternal age hypertension, it is also associated with albumin levels. Pregnant women over 35 years of age will have lower albumin levels and experience an almost double increased risk of hypertension in primiparous and multipara (Ding et al, 2021). Moreover, young people less than 19 years old can also escalate the risk of low albumin levels (Deng et al, 2021).…”