Lipogenesis in the Human Sebaceous Gland: Glycogen and Glycerophosphate are Substrates for the Synthesis of Sebum Lipids

Abstract

The lipid class compositions of freshly isolated and overnight maintained human sebaceous glands were determined using high performance thin layer chromatography and were found to be broadly similar. The lipid classes identified in freshly isolated glands were broadly similar to those generated from various radiolabeled precursors in vitro, although lower amounts of wax/sterol esters and cholesterol were observed in vitro. We determined the glycogen content of sebaceous glands and showed that during their incubation with several radiolabeled substrates, with the exception of [U-14C]glucose, significant glycogen breakdown occurred, thus providing acetyl-CoA and NADPH that could affect the pattern of lipids synthesized. We examined glycogen-depleted glands and found that their rates and pattern of lipogenesis resemble that of nondepleted glands, except that the squalene/triacylglycerides ratio for acetate and glutamine doubled from 1.6:1 to 3.4:1 and from 0.7:1 to 1.4:1, respectively. We have shown that exogenous glycerol reduces the squalene/triacylglycerides ratio from acetate from 3.4:1 to 1.7:1, suggesting that glycogen-derived glycerophosphate is important in triacylglycerides synthesis from acetate. Moreover, glands express a glycerokinase activity that may fully account for the rate of triacylglycerides synthesis seen in vitro. We conclude that glycerophosphate generation may be as important as NADPH generation in explaining the directing effects of different substrates within the sebaceous gland.

Family History and Risk of Hair Loss

“…For the purposes of this analysis, we chose to use the independent observer’s assessment of hair loss because independent observers have been shown to be more objective at rating hair loss than subjects [19]. The degree of hair loss was classified into two categories of ‘no hair loss’ and ‘hair loss’.…”

Squalene Chemistry and Biology

“…Experiments based on the incorporation of radiolabeled acetate, have demonstrated that the SG possesses the capacity to synthesize lipids de novo (Summerly and Woodbury 1971;Guy et al 1999). Based on the patterns of lipids synthesized from different exogenous substrates, it has been suggested that NADPH was a limiting and directing factor of the sebaceous lipids biosynthesis in isolated SG (Middleton et al 1988;Downie and Kealey 1998). Exogenous radiolabeled glucose, a good source of NADPH, favors TG synthesis, whereas exogenous radiolabeled acetate, a poor source of NADPH, is in favor of squalene.…”

“…Following glycogen breakdown, glycerophosphate is as important as NADPH in governing the sebaceous lipogenesis. Squalene synthesis is favored over TG when acetate and glutamine are the substrates, independently on the glycogen status of the gland (Downie and Kealey 1998).…”

“…Nevertheless, cholesterol itself does not take part in the sebogenesis as its synthesis is interrupted at the level of squalene, which instead accumulates in the lipid droplets. NADPH is implicated in the synthesis of cholesterol from squalene, however other factors seem to determine a low cholesterol/squalene ratio and are to be searched among those regulating the activity of squalene epoxidase and downstream enzymes (Downie and Kealey 1998). Detection of low levels of 2,3-squalene oxide in sebum might be due to a partial activity of the squalene monooxygenase or to nonenzymatic squalene oxidation.…”

Estudo das mudanças quali e quantitativas da participação de ácidos graxos no sebo de pacientes com acne inflamatória, graus II ou III, em uso sistêmico de limeciclina e/ou suplementação oral à base de ácidos linoleico, gamalinolênico

“…Sabe-se que o colesterol é obtido a partir do esqualeno (Downie;Kealey, 1998;Pappas et al, 2009). O esqualeno, juntamente com os ésteres de cera, têm origem na glândula sebácea; os TG originam-se tanto nas glândulas sebáceas quanto na epiderme; os AGL são obtidos pela lipólise bacteriana dos TG ou por esterases presentes no ducto sebáceo; por fim, o colesterol e seus ésteres têm origem epidérmica, predominantemente (Cotterill et al, 1972 Quanto maior o tamanho das GS, maior a participação lipídica do esqualeno na secreção do SB.…”