tetano
Editor, Senior Moderator
Eur J Clin Invest
. 2026 May;56(5):e70215.
doi: 10.1111/eci.70215.
FNDC4 and FNDC5 Attenuate SARS-CoV-2 S1-Induced Inflammatory Responses in Human Adipose Tissue
Gabriela Neira[SUP] 1 2 3 [/SUP], Julia Hernández-Castañeda[SUP] 1 [/SUP], Victoria Catalán[SUP] 1 2 3 4 [/SUP], Sara Becerril[SUP] 1 2 3 4 [/SUP], Marina Martín[SUP] 5 [/SUP], Víctor Valentí[SUP] 2 3 4 6 [/SUP], Rafael Moncada[SUP] 2 3 4 7 [/SUP], Camilo Silva[SUP] 2 3 4 8 [/SUP], Javier Gómez-Ambrosi[SUP] 1 2 3 4 [/SUP], Javier Escalada[SUP] 2 3 4 8 [/SUP], Gema Frühbeck[SUP] 1 2 3 4 8 [/SUP], Amaia Rodríguez[SUP] 1 2 3 4 [/SUP]
Affiliations
Background: Adipose tissue is recognised as a SARS-CoV-2 reservoir and potential infection site. We herein characterised SARS-CoV-2 entry points in visceral (VAT) and subcutaneous (SAT) adipose tissue from people with obesity and determined whether the adipo-myokines FNDC4 and FNDC5 modulate SARS-CoV-2 spike glycoprotein subunit 1 (S1)-induced inflammation in adipocytes and macrophages.
Methods: Plasma concentrations of FNDC4, FNDC5 and angiotensin-converting enzyme 2 (ACE2) were measured in 183 participants with obesity and normal weight. Expression of SARS-CoV-2 host cell entry receptors was analysed in paired VAT and SAT biopsies (n = 121). The effects of FNDC4 and FNDC5 on S1-induced inflammatory responses were evaluated in vitro using human visceral adipocytes and THP-1-derived macrophages.
Results: Obesity was associated with higher circulating ACE2 and increased expression of SARS-CoV-2 entry receptors (ACE2, CD147, DPP4 and neuropilin-1) in VAT, whereas plasma FNDC4 and FNDC5 levels were reduced. FNDC4, FNDC5 and ACE2 co-localised with macrophage populations in VAT, and FNDC4 and FNDC5 transcripts positively correlated with genes involved in viral entry and priming. Both adipo-myokines attenuated S1-induced M1 macrophage polarisation and HMGB1 secretion and reduced HMGB1 expression in adipocytes.
Conclusion: Reduced FNDC4 and FNDC5 levels in obesity may amplify SARS-CoV-2 S1-induced inflammatory responses in VAT macrophages and adipocytes.
Keywords: ACE2; SARS‐CoV‐2; adipose tissue inflammation; myokines; obesity.
. 2026 May;56(5):e70215.
doi: 10.1111/eci.70215.
FNDC4 and FNDC5 Attenuate SARS-CoV-2 S1-Induced Inflammatory Responses in Human Adipose Tissue
Gabriela Neira[SUP] 1 2 3 [/SUP], Julia Hernández-Castañeda[SUP] 1 [/SUP], Victoria Catalán[SUP] 1 2 3 4 [/SUP], Sara Becerril[SUP] 1 2 3 4 [/SUP], Marina Martín[SUP] 5 [/SUP], Víctor Valentí[SUP] 2 3 4 6 [/SUP], Rafael Moncada[SUP] 2 3 4 7 [/SUP], Camilo Silva[SUP] 2 3 4 8 [/SUP], Javier Gómez-Ambrosi[SUP] 1 2 3 4 [/SUP], Javier Escalada[SUP] 2 3 4 8 [/SUP], Gema Frühbeck[SUP] 1 2 3 4 8 [/SUP], Amaia Rodríguez[SUP] 1 2 3 4 [/SUP]
Affiliations
- PMID: 42047312
- PMCID: PMC13123202
- DOI: 10.1111/eci.70215
Background: Adipose tissue is recognised as a SARS-CoV-2 reservoir and potential infection site. We herein characterised SARS-CoV-2 entry points in visceral (VAT) and subcutaneous (SAT) adipose tissue from people with obesity and determined whether the adipo-myokines FNDC4 and FNDC5 modulate SARS-CoV-2 spike glycoprotein subunit 1 (S1)-induced inflammation in adipocytes and macrophages.
Methods: Plasma concentrations of FNDC4, FNDC5 and angiotensin-converting enzyme 2 (ACE2) were measured in 183 participants with obesity and normal weight. Expression of SARS-CoV-2 host cell entry receptors was analysed in paired VAT and SAT biopsies (n = 121). The effects of FNDC4 and FNDC5 on S1-induced inflammatory responses were evaluated in vitro using human visceral adipocytes and THP-1-derived macrophages.
Results: Obesity was associated with higher circulating ACE2 and increased expression of SARS-CoV-2 entry receptors (ACE2, CD147, DPP4 and neuropilin-1) in VAT, whereas plasma FNDC4 and FNDC5 levels were reduced. FNDC4, FNDC5 and ACE2 co-localised with macrophage populations in VAT, and FNDC4 and FNDC5 transcripts positively correlated with genes involved in viral entry and priming. Both adipo-myokines attenuated S1-induced M1 macrophage polarisation and HMGB1 secretion and reduced HMGB1 expression in adipocytes.
Conclusion: Reduced FNDC4 and FNDC5 levels in obesity may amplify SARS-CoV-2 S1-induced inflammatory responses in VAT macrophages and adipocytes.
Keywords: ACE2; SARS‐CoV‐2; adipose tissue inflammation; myokines; obesity.