Adipocyte differentiation of 3T3-L1 cells under tenofovir alafenamide, tenofovir disoproxil fumarate, and integrase strand transfer inhibitors selective challenge: an in-vitro model

Perna, Angelica; Carleo, Maria Aurora; Mascolo, Silvia; Guida, A.; Contieri, Marcella; Sellitto, Carmine; Hay, Eleonora; Blasiis, Paolo De; Lucariello, Angela; Guerra, Germano; Baldi, Alfonso; Luca, Antonio De; Maggi, Paolo; Esposito, Vincenzo

doi:10.1097/qad.0000000000003455

Cited by 3 publications

(2 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, the same group compared control, SIV-infected untreated and SIV-infected ART-controlled (with DTG/TDF/FTC) macaques [28] and confirmed the ability of ART to increase the expression of genes involved in adipogenesis, fibrosis and hypoxia. In murine 3T3-L1 adipocytes, INSTIs globally increased adipogenesis and the expression of a fibroblastic factor ER-TR7, possibly participating to fibrosis [29], confirming previous studies. However, in SGBS adipocytes, with a high proliferative potential, an experienced group did not observe any striking effect of different INSTIs on adipocyte differentiation and function, except at high drug concentrations [30].…”

Section: Mechanismssupporting

confidence: 89%

“…Regarding TDF and TAF, only a few studies have directly analyzed their impact on AT and suggested increased mitochondrial toxicity. In one study [29], both TDF and TAF, used at the same dosage, inhibited adipogenesis. This differs from the clinical situation, in which the intracellular concentration of the active metabolite tenofovir-diphosphate is markedly higher with TAF than with TDF.…”

Section: Mechanismsmentioning

confidence: 99%

See 1 more Smart Citation

Recent data on the role of antiretroviral therapy in weight gain and obesity in persons living with HIV

Capeau,

Lagathu,

Béréziat

2023

Current Opinion in HIV and AIDS

View full text Add to dashboard Cite

Purpose of review Antiretroviral therapy (ART) has long been implicated in fat alterations and weight variations leading to cardiometabolic consequences. Recent largely prescribed antiretrovirals (ARVs) from the integrase-strand-transfer-inhibitor (INSTI) class have been associated with excessive weight gain/obesity in a minority of persons with HIV (PWH). As well, in the nucleoside reverse transcriptase inhibitors (NRTI) class, tenofovir-alafenamide (TAF), often replacing tenofovir-disoproxil-fumarate (TDF), has been associated with weight gain, a worrying concern in the present worldwide obesogenic environment. The respective role of the different ARV, the risk factors and the mechanisms remain questionable. Recent findings The INSTIs dolutegravir (DTG) and bictegravir (BIC) and TAF have a proper effect on weight gain, while efavirenz (EFV) and TDF inhibit it. These effects are reported in ART-naïve PWH, in addition to weight gain resulting from the return to health process, and in ART-controlled PWH. Also, INSTIs induce weight gain in adolescents and excessive weight gain during pregnancy. The effects of INSTIs and TAF are additive. Their trajectory differs. Most of the weight gain is observed during the initial 12-month period. The main risk factors are low CD4+ and high viral load (VL) in ART-naïve PWH, Black race or originating from some African countries and female gender. The role of age and BMI differs between studies. The reversibility of the effect of INSTI and TAF appears limited. Regarding the mechanisms, the INSTIs can directly alter adipose tissue in particular through inhibition of fat beiging, resulting in fat fibrosis and hypertrophy. Macrophage infiltration is decreased. The mechanisms explaining the opposite effects of TDF and TAF remain elusive. Summary The specific impact of DTG, BIC and TAF on weight gain/obesity in PWH is confirmed in different populations independently of the weight limiting effect of EFV and TDF. ART-linked excessive weight gain is uncommon. African origin and female sex are risk factors that need to be considered. The mechanisms are better understood for INSTIs but unknown for TDF/TAF. The reversibility of weight gain/obesity when stopping INSTI or TAF remains limited.

show abstract

Section: Mechanismssupporting

confidence: 89%

Section: Mechanismsmentioning

confidence: 99%

Recent data on the role of antiretroviral therapy in weight gain and obesity in persons living with HIV

Capeau,

Lagathu,

Béréziat

2023

Current Opinion in HIV and AIDS

View full text Add to dashboard Cite

show abstract

Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function

Quesada-López,

Cereijo,

Blasco-Roset

et al. 2024

Biochemical Pharmacology

View full text Add to dashboard Cite

Dietary regimens appear to possess significant effects on the development of combined antiretroviral therapy (cART)-associated metabolic syndrome

Chege,

Mwangi,

Githinji

et al. 2024

PLoS ONE

View full text Add to dashboard Cite

Introduction This study investigated the interactions between a low protein high calorie (LPHC) diet and an integrase inhibitor-containing antiretroviral drug regimen (INI-CR)in light of evidence suggesting that the initiation of cART in patients with poor nutritional status is a predictor of mortality independent of immune status. Methods Freshly weaned Sprague Dawley rats (120) were randomized into the standard, LPHC and normal protein high calorie (NPHC) diet groups (n = 40/group) initially for 15 weeks. Thereafter, experimental animals in each diet group were further randomized into four treatment sub-groups (n = 10/group) Control (normal saline), group 1(TDF+3TC+DTG and Tesamorelin), group 2 (TDF+3TC+DTG), and Positive control (AZT+3TC+ATV/r) with treatment and diets combined for 9 weeks. Weekly body weights, fasting blood glucose (FBG), oral glucose tolerance test (OGTT); lipid profiles, liver weights, hepatic triglycerides and adiposity were assessed at week 24. Results At week 15, body weights increased between the diet group in phase 1(standard 146 ± 1.64 vs. 273.1 ± 1.56 g), (NPHC, 143.5 ± 2.40 vs. 390.2 ± 4.94 g) and (LPHC, 145.5 ± 2.28 g vs. 398.3 ± 4.89 g) (p< 0.0001). A similar increase was noted in the FBG and OGTT (p< 0.0001). In phase 2, there was an increase in FBG, OGTT, body weights, lipid profile, liver weights, hepatic triglycerides, adiposity and insulin levels in group 2 and positive control in both NPHC and LPHC diet groups (p<0.0001). Growth hormone levels were decreased in Tesamorelin-free group 2 and positive control in both NPHC and LPHC (p< 0.0001). Conclusions The obesogenic activities of the LPHC diet exceeded that of the NPHC diet and interacted with both integrase-containing and classical cART drug regimens to reproduce cART associated metabolic dysregulation. The effects were however reversed by co-administration with tesamorelin, a synthetic growth hormone releasing hormone analogue.

show abstract

Adipocyte differentiation of 3T3-L1 cells under tenofovir alafenamide, tenofovir disoproxil fumarate, and integrase strand transfer inhibitors selective challenge: an in-vitro model

Cited by 3 publications

References 56 publications

Recent data on the role of antiretroviral therapy in weight gain and obesity in persons living with HIV

Recent data on the role of antiretroviral therapy in weight gain and obesity in persons living with HIV

Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function

Dietary regimens appear to possess significant effects on the development of combined antiretroviral therapy (cART)-associated metabolic syndrome

Contact Info

Product

Resources

About