Lipid droplets in felid kidneys: prevalence and composition by lipidomics

An accepted and common phenotypic curiosity of Felidae is the presence of intracytoplasmic lipid droplets in renal proximal tubule epithelial cells (RPTEC), also frequently 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 CKD. Despite domestic felids having a high incidence of CKD as they age, no study has fully characterised feline RPTEC lipid droplets in the context of CKD. Here, we first characterised the incidence of RPTEC lipid in domestic cat (with/without CKD or chronic interstitial nephritis) versus domestic dog and Scottish Wildcat, across a wide age range. Felids (domestic, wildcat) consistently had greater renal lipid content than dogs at all ages studied. Intracytoplasmic lipid extraction with chromatography, fatty acid characterisation and mass spectrometry-based lipidomics revealed unusual presence of a panoply of novel lipids found only in domestic cat: lipids were primarily modified (i.e. less polar) ether-soluble triacylglycerols including monoalkyldiacylglycerols (MADAGs) and other branched-chain fatty acids. We suggest common presence of such rare lipid species in tubular lipid droplets in domestic cat 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.