Mitochondria isolated from lipid droplets of white adipose tissue reveal functional differences based on lipid droplet size.

Recent studies in brown adipose tissue (BAT) described a unique subpopulation of mitochondria bound to lipid droplets (LDs), which were termed PeriDroplet Mitochondria (PDM). PDM can be isolated from BAT by differential centrifugation and salt washes. Contrary to BAT, this approach has so far not led to the successful isolation of PDM from white adipose tissue (WAT). Here, we developed a method to isolate PDM from WAT with high yield and purity by an optimized proteolytic treatment that preserves the respiratory function of mitochondria. Using this approach, we show that, contrary to BAT, WAT PDM have lower respiratory and ATP synthesis capacities compared with WAT cytoplasmic mitochondria (CM). Furthermore, by isolating PDM from LDs of different sizes, we found a negative correlation between LD size and the respiratory capacity of their PDM in WAT. Thus, our new isolation method reveals tissue-specific characteristics of PDM and establishes the existence of heterogeneity in PDM function determined by LD size.

SARS-CoV-2 infection as a model to study the effect of cinnamaldehyde as adjuvant therapy for viral pneumonia.

BACKGROUND: The recent pandemic outbursts, due to SARS-CoV-2, have highlighted once more the central role of the inflammatory process in the propagation of viral infection. The main consequence of COVID-19 is the induction of a diffuse pro-inflammatory state, also defined as a cytokine storm, which affects different organs, but mostly the lungs. We aimed to prove the efficacy of cinnamaldehyde, the active compound of cinnamon, as an anti-inflammatory compound, able to reduce SARS-CoV-2 induced cytokine storm. RESULTS: We enrolled 53 COVID-19 patients hospitalized for respiratory failure. The cohort was composed by 39 males and 13 females, aged 65.0 ± 9.8 years. We reported that COVID-19 patients have significantly higher IL-1ß and IL-6 plasma levels compared to non-COVID-19 pneumonia patients. In addition, human mononuclear cells (PBMCs) isolated from SARS-CoV-2 infected patients are significantly more prone to release pro-inflammatory cytokines upon stimuli. We demonstrated, using in vitro cell models, that macrophages are responsible for mediating the pro-inflammatory cytokine storm while lung cells support SARS-CoV-2 replication upon viral infection. In this context, cinnamaldehyde administration significantly reduces SARS-CoV-2-related inflammation by inhibiting NLRP3 mediated IL-1ß release in both PBMCs and THP-1 macrophages, as well as viral replication in CaLu-3 epithelial cells. Lastly, aerosol-administered cinnamaldehyde was able to significantly reduce IL-1ß release in an in vivo lung-inflammatory model. CONCLUSION: The obtained results suggest the possible use of cinnamaldehyde as a co-adjuvant preventive treatment for COVID-19 disease together with vaccination, but also as a promising dietary supplement to reduce, more broadly, viral induced inflammation.