Differences in the Proteome of Cardiac and Perigonadal Adipose Tissue-Derived Adipoids

Background: Adipose tissue (AT) is an endocrine and immunological organ. Cardiac AT (cAT) is a specific fat depot due to its direct contact with the myocardium and coronary arteries. Physiological cAT protects the heart from mechanical stress, secretes anti-inflammatory adipokines and captures free fatty acids. Under pathological conditions, proinflammatory and profibrotic cytokines are released, causing inflammation, and an exaggerated immune response, which may be associated with cardiovascular disease (CVD). However, until now cAT is poorly characterized especially with regards to the other fat depots. This study aims to better understand cAT by comparing proteome composition to perigonadal AT (pAT) using immune-competent adipoids (Ad).

Methods: We isolated cAT and pAT from male Wistar rats and obtained the stromal vascular fraction (SVF). From SVF, we generated spheroids and further differentiated them into Ad. For Ad characterization differences in lipid droplet quantity and morphology were studied using immunofluorescence. Proteome composition of the cAT and pAT-derived Ad (cAd, pAd) was investigated by mass spectrometry and proteins were classified by their function using Gene Ontology (GO) term analysis.

Results: Neutral lipid staining of cAd show multilocular lipid droplets similar to beige AT, while pAd have monolocular lipid droplets typical for white AT, demonstrating the different phenotypes. In proteomic analysis, we identified a total of 1174 proteins, with 86 unique to cAd and 154 to pAd. Both depots contained 934 proteins, but with significant differences in quantities, indicating different functions. For instance, cAd had significantly higher quantity of glutamate dehydrogenase 1 which plays a key role in energy homeostasis and long-chain-fatty-acid-CoA ligase 1, which plays a key role in lipid biosynthesis and fatty acid degradation. In contrast, pAd contain more proteins involved in cholesterol homeostasis (such as alcohol dehydrogenase 4, acyl-CoA synthetase short chain family member 2).

Conclusion: This study reveals significant differences between the proteome of cAd and pAd, such as varying quantities of key lipid biosynthesis proteins, suggesting distinctive disparities in fat depot lipid metabolism. These findings correlate with disparities in lipid droplet morphology between cAd and pAd. Consequently, cAd replicates unique features of cardiac fat, making it a valuable tool for exploring cAT's role in CVD leading to targeted therapies and prevention strategies.

 

MissingLinkText

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
13 February 2024