Lipid droplets in felid kidneys: prevalence and composition by lipidomics

Introduction: An accepted and common phenotypic curiosity of Felidae is the presence of intracytoplasmic lipid droplets in renal proximal tubule epithelial cells (RPTEC), also frequently observed in urine (lipuria). Both outcomes are currently considered, and taught, as incidental - without obvious pathophysiological consequence. This contrasts markedly with clinical (human) medicine, where lipid vacuoles in RPTEC are usually associated with metabolic or chronic disease, such as chronic kidney disease (CKD). Despite domestic felids having a high incidence of CKD with advancing age, no study has fully characterized feline RPTEC lipid droplets in the context of CKD. Methods: In this study, we first characterized the incidence of RPTEC lipid in domestic cats (with/without CKD or chronic interstitial nephritis) versus domestic dogs and Scottish Wildcats, across a wide age range, using a number of lipidomic approaches (chromatography, fatty acid characterization, mass spectrometry). Results: Felids (domestic and wildcat) consistently had greater renal lipid content than dogs at all ages studied. Intracytoplasmic lipid extraction revealed a panoply of novel lipids found only in domestic cats: lipids were primarily modified (i.e., less polar) ether-soluble triacylglycerols, including mono-alkyl-diacylglycerols (MADAGs) and other likely, branched-chain fatty acids. Discussion: We suggest that the common presence of such rare lipid species in tubular lipid droplets in domestic cats reflects an aspect of felid biology that parallels age-related disease prevalence, in particular, being associated with the aetiopathogenesis of chronic renal interstitial nephritis (CIN) - a hallmark of CKD in felids.