Dissecting lipid metabolism in meibomian glands of humans and mice: An integrative study reveals a network of metabolic reactions not duplicated in other tissues

Abstract

Lipids comprise the bulk of the Meibomian gland secretion (meibum) which is produced by meibocytes. Complex arrays of lipogenic reactions in Meibomian glands, which we collectively call meibogenesis, have not been explored on molecular level yet. Our goals were to elucidate the possible biosynthetic pathways that underlie generation of meibum, reveal similarities in, and differences between, lipid metabolism in Meibomian glands and other organs and tissues, and integrate Meibomian gland studies into the field of general metabolomics. Specifically, we have conducted detailed analyses of human and mouse specimens using genomic, immunohistochemical, and lipidomic approaches. Among equally highly expressed genes found in Meibomian glands of both species were those related to fatty acid elongation, branching, desaturation, esterification, reduction of fatty acids to alcohols, and cholesterol biosynthesis. Importantly, corresponding lipid products were detected in meibum of both species using lipidomic approaches. For the first time, a cohesive, unifying biosynthetic scheme that connects genomic, lipidomic, and immunohistochemical observations is outlined and discussed.

Meibomian glands, meibum, and meibogenesis

“…Data of Nicolaides et al (Nicolaides et al, 1981; Nicolaides et al, 1984) further advanced our understanding of FA and FAl found in meibomian lipids as very long chain and/or branched moieties. These observations were later corroborated in the studies of individual intact WE (Butovich et al, 2012a) and whole human meibum [(Butovich et al, 2016)].…”

“…It seems that further efforts of this nature, without addressing specific unanswered questions, would produce progressively less new information due to the universal law of diminishing returns. For comparison purposes, the lipid composition of a related secretion, namely sebum (Butovich et al, 2016) (Thiboutot, 2004) (Picardo et al, 2009) (Nakahara et al, 2015), is also presented in Table 1, from which one can conclude that sebum and meibum substantially differ from each other.…”

“…On the other hand, the main fatty acid chains in human skin acyl-Cer can be as long as C 36 (Farwanah et al, 2005), which is on par with lipids of meibum. However, the overall lipid profile of meibum (Butovich et al, 2016) is very different from that of skin (Farwanah et al, 2005; McMahon et al, 2007): Cer and acyl-Cer (including those of the ELC nature) are major constituents of epidermis of both humans and mice, while being virtually nonexistent in normal human meibum and sebum. Sebum lipids are also different from meibum: the former, unlike meibum, are dominated by four lipid classes – acylglycerols (mostly TAG), WE, FFA, and Sql.…”

“…Considering the extremely diverse and complex nature of meibomian lipids, in a recent publication (Butovich et al, 2016) we have summarized major features that, from our standpoint, define meibum as a unique fusion of various compounds whose composition is, apparently, not duplicated in other secretions, cells, and tissues. These features are shown in Table 2.…”

“…To facilitate the progress in the area of meibogenesis studies, we initiated a pilot project which was to integrate our knowledge of human and mouse meibomian lipidomes with newly obtained data on gene and protein expression patterns in human and mouse meibomian glands (Butovich et al, 2016). Human and mouse meibomian lipids were found to be very similar to each other, in terms of lipid classes and individual lipid species.…”