Cholesterol made in skin?

I wonder, could frequent skin washing with strong detergents or EFAD
increase blood total cholesterol? Both disrupt the cutaneous barrier
function (the latter due to "LA deficiency"):

J Invest Dermatol. 1986 Nov;87(5):588-91.

Effect of essential fatty acid deficiency on cutaneous sterol
synthesis.

Feingold KR, Brown BE, Lear SR, Moser AH, Elias PM.

The fact that the skin is a major site of total body sterologenesis,
coupled both with the apparent absence of low density lipoprotein
receptors on keratinocytes and with the lack of influence of serum
cholesterol on epidermal sterologenesis, has created the impression
that epidermal lipid synthesis might be autonomous, i.e.,
nonregulatable. Recent studies have shown, however, that disruption of
cutaneous barrier function with acetone or detergents stimulates
epidermal sterologenesis (J Lipid Res 26:418-427, 1985). To correlate
further sterologenesis with barrier function, we measured de novo
synthesis of cholesterol and total nonsaponifiable lipids in essential
fatty acid-deficient (EFAD) hairless mice. Animals with defective
barrier function, manifested by abnormal transepidermal water loss,
demonstrated a 2-fold increase in epidermal cholesterol and total
nonsaponifiable lipid synthesis over controls while synthesis in the
dermis was unchanged. Epidermal sterologenesis in EFAD animals,
repleted with linoleic acid either systematically or topically,
returned toward normal as barrier function improved. Moreover, plastic
occlusion of EFAD mouse skin normalized epidermal sterologenesis at 1
and 3 days. These results provide further evidence that epidermal
sterologenesis is not entirely autonomous, and can be regulated by
water barrier requirements.
PMID: 3772153


J Invest Dermatol. 1992 Aug;99(2):216-20.

Epidermal HMG CoA reductase activity in essential fatty acid
deficiency: barrier requirements rather than eicosanoid generation
regulate cholesterol synthesis.

Proksch E, Feingold KR, Elias PM.
Department of Dermatology, University of Kiel, Germany.

We showed previously that the activity of 3-hydroxy-3-methylglutaryl
coenzyme A (HMG CoA) reductase, the rate-limiting enzyme of
cholesterol biosynthesis, increases after both barrier disruption with
organic solvents and in essential fatty acid deficiency (EFAD). Here,
we treated EFAD hairless mice with linoleic acid, columbinic acid
(C18: 3, n-6, trans; not metabolizable to known regulatory
eicosanoids), prostaglandin E2 (PGE2), or latex occlusion, and
determined transepidermal water loss (TEWL), epidermal protein
content, and epidermal HMG CoA reductase activity. Increased TEWL
rates in EFAD were accompanied by increased HMG CoA reductase activity
(+130%, n = 6, p less than 0.01) and protein content (+69%; n = 6, p
less than 0.025). Artificial restoration of the barrier by occlusion
reduced the increase in enzyme activity and protein content toward
normal, but barrier function, measured immediately after removal of
the latex wrap, deteriorated further (TEWL: two-fold greater than EFAD
unoccluded; p less than 0.01). Topical applications of either
linoleate or columbinate (but not PGE2), normalized barrier function,
HMG CoA reductase activity, and protein content. These results show
that a) barrier function modulates HMG CoA reductase activity; b)
reduction of cholesterol synthesis with occlusion results in a further
deterioration in barrier function, suggesting that increased synthesis
is a protective homeostatic response; and c) the barrier abnormality
reflects a requirement for specific fatty acids for the barrier rather
than resulting from epidermal hyperplasia or decreased prostaglandin
generation.
PMID: 1629633


PMID: 9406821


J Lipid Res. 1990 Nov;31(11):2009-17.

Combined (n-3 and n-6) essential fatty deficiency is a potent
modulator of plasma lipids, lipoprotein composition, and lipolytic
enzymes.

Levy E, Thibault L, Garofalo C, Messier M, Lepage G, Ronco N, Roy CC.
Centre de Recherche Pédiatrique, Hôpital Ste-Justine, Montréal,
Québec, Canada.

Essential fatty acids (EFA) are important structural and functional
components of cell membranes. Their deficiency has been associated
with several clinical and biochemical abnormalities. In the present
study, the lipid profile as well as the concentration, composition,
and metabolism of lipoproteins were examined in rats rendered EFA-
deficient over a period of 12 weeks. Changes in plasma fatty acids
mainly induced an increase of palmitoleic (16:1 n-7) and
eicosatrienoic (20:3 n-9) acids, while linoleic (18:2 n-6),
arachidonic (20:4 n-6), linolenic (18:3 n-3), and docosahexaenoic
(22:6 n-3) acids were decreased. The results show increased
concentrations of free fatty acids (FFA) (P less than 0.001),
triglycerides (P less than 0.001), total cholesterol (P less than
0.02), free cholesterol (P less than 0.005), and phospholipids (P less
than 0.05) when compared to pair-fed controls. Similar levels of
cholesteryl esters were found in the two groups, and lecithin:
cholesterol acyltransferase activity (nmol/100 microliters plasma per
h) (8.98 +/- 1.44 vs 8.72 +/- 0.50) did not differ. On the other hand,
postheparin extrahepatic lipoprotein lipase (LPL) activity was
significantly (P less than 0.002) decreased (5.96 +/- 0.29 vs 7.29 +/-
0.68 mumol FFA/ml per h) and could account for the
hypertriglyceridemia as well for the relative triglyceride enrichment
of very low density lipoprotein, intermediate density lipoprotein, and
low density lipoprotein particles. This enzymatic depletion of LPL was
mainly due to the adipose tissue, since a higher level (P less than
0.001) of hepatic lipase (325.8 +/- 16.0 vs 130.8 +/- 9.5 nmol FFA/mg
protein per h) was found in liver acetone powder extracts.(ABSTRACT
TRUNCATED AT 250 WORDS)
PMID: 2086700

When you say "EFAD" disrupting cutaneous barrier function, I assume
you mean that not enough Mead acid (or AA) can be generated, for
whatever reason, correct? If not, I have personally refuted your
claim, because I don't have any problems with this function.

On May 10, 3:41 am, monty1...@lycos.com wrote:
> When you say "EFAD" disrupting cutaneous barrier function, I assume
> you mean that not enough Mead acid (or AA) can be generated, for
> whatever reason, correct? If not, I have personally refuted your
> claim, because I don't have any problems with this function.

It seems that rather the shorter PUFAs such as linoleic acid (LA,
Omega-6) or MUFAs such as oleic acid (Omega-9 precursor to Mead acid)
play a role in the barrier function:

Arch Dermatol Res. 1999 Jan;291(1):47-53.

Fatty acid uptake by cultured human keratinocytes grown in medium
deficient in or supplemented with essential fatty acids.

Schürer NY, Rippke F, Vogelsang K, Schliep V, Ruzicka T.
Department of Dermatology, University of Düsseldorf, Germany.

Epidermal linoleic acid, i.e. essential fatty acid (EFA), is essential
for cutaneous barrier function. Cultured human keratinocytes,
routinely used for studies of lipid metabolism, are grown in a
keratinocyte serum-free medium (KSFM), under conditions that reveal
EFA-deficient cells. Here, fatty acid (FA) uptake was analysed in
human adult keratinocytes grown either under EFA-deficient conditions
[KSFM supplemented with 10% FCS (A) or 1% UltroserG (B)] or EFA-
supplemented conditions [KSFM supplemented with a devised FA cocktail
(C) or evening primrose oil (D)]. The FA composition of the total
cellular lipid and major lipid fractions was analysed by gas
chromatography. Cells grown with supplements A or B balanced their EFA-
deficient state primarily with oleic acid. Cells grown with
supplements C or D normalized to the epidermal FA composition in vivo
with raised linoleic and lower oleic acid contents. When cells were
grown longer than 48 h with supplements C or D decreased cell growth
was observed. FA uptake was curvilinear with preference for linoleic
over oleic acid under all culture conditions. The uptake of linoleic
acid by cells cultured with supplement B was twice the uptake of those
cultured with supplement A, while the uptake of oleic acid was similar
under both culture conditions. Oleic acid uptake of cells cultured
with supplement C or D was lower. These results show that the uptake
of linoleic, but not that of oleic acid, is influenced by the
extracellular FA composition, and that EFA-supplemented keratinocytes
compared to EFA-deficient cells might serve as an in vitro model for
the study of EFA metabolism.
PMID: 10025727


J Invest Dermatol. 1980 Apr;74(4):230-3.

The permeability barrier in essential fatty acid deficiency: evidence
for a direct role for linoleic acid in barrier function.

Elias PM, Brown BE, Ziboh VA.

Essential fatty acid (EFA) deficient rodents demonstrate abnormal
epidermal permeability barrier function and differentiation, defects
which can be corrected by either topical or systemic administration of
linoleic acid. Since linoleic acid is a precursor of prostaglandins,
correction of the defect in barrier function may either reflect a
prostaglandin-mediated return toward normal epidermal differentiation,
or, instead, a direct effect of linoleic acid. To test these
possibilities severely EFA-deficient mice were pretreated daily with
indomethacin and/or 5,8,11,14-eicosatetrayeonic acid, and then placed
on normal (lineolic acid-supplemented) diets. Endogenous formation of
prostaglandin E2 was determined by thin-layer chromatography after
transformation into prostaglandin B2 with ethanolic-hydrochloric acid.
Animals treated with both indomethacin and TYA DEMONSTRATED
SUBSTANTIAL REDUCTIONS IN PROSTAGLANDIN E2 levels in liver and skin.
Animals replenished with linoleic acid invariably demonstrated a rapid
return of barrier function toward normal whether or not they were
blockaded, while nonreplenished animals, with or without inhibition of
prostaglandin biosynthesis, demonstrated continued deterioration in
barrier function. In other experiments, topically applied linoleic
acid rapidly reversed the defect in barrier function at the sites of
application prior to systemic correction of the EFA deficient state.
These results suggest that: (1) defective cutaneous barrier function
in EFA deficiency can be corrected locally without prior systemic
reversal of the deficiency state; and (2) that linoleic acid may play
a direct role in the epidermal permeability barrier independent of its
role in prostaglandin metabolism.
PMID: 7373078


J Clin Invest. 1994 Jul;94(1):89-96.

Pseudo-acylceramide with linoleic acid produces selective recovery of
diminished cutaneous barrier function in essential fatty acid-
deficient rats and has an inhibitory effect on epidermal hyperplasia.

Imokawa G, Yada Y, Higuchi K, Okuda M, Ohashi Y, Kawamata A.
Tochigi Research Laboratories, Kao Corporation, Japan.

Pseudo-acylceramides with different acyl properties were investigated
for their capacity to restore diminished barrier function in essential
fatty acid-deficient rats. Daily topical applications of synthetic
pseudo-acylceramides containing ester-linked linoleic acid caused a
dose-dependent, significant reduction of transepidermal water loss
(TEWL). Both other pseudo-acylceramides with ester-linked oleic acid
or saturated alkyl chains and ordinary ceramides exhibited a poor
effect on recovery of TEWL. Furthermore, pseudoceramide containing
ether-linked linoleic acid, which is biologically inactive in terms of
degradation by hydrolytic enzymes, also induced a significant and
similar increase in the barrier function. This restoration of barrier
function by pseudo-acylceramides with linoleic acid was accompanied by
suppressed DNA synthesis in the EFAD rat epidermis. In UVB-irradiated
guinea pig skin, topical applications of the pseudo-acylceramides with
linoleic acid immediately after the exposure significantly reduced
epidermal hyperplasia, secondary to markedly diminished barrier
disruption, whereas linoleic acid itself did not. A comparison of both
the anti-hyperplasia and the barrier recovery effects in the series of
pseudo-ceramide derivatives examined revealed that the suppressive
effect on the induced epidermal hyperplasia was paralleled by the
recovery of the barrier defect in EFAD rats. These findings directly
suggest that acylceramide with an ester-linked linoleic acid has an
essential role in the epidermal permeability barrier.
PMID: 8040295


Br J Dermatol. 1976 Jan;94(1):13-21.

The repair of impaired epidermal barrier function in rats by the
cutaneous application of linoleic acid.

Prottey C, Hartop PJ, Black JG, McCormack JI.

Epidermal barrier function in rats was experimentally impaired by two
separate means, namely, by rendering the animals deficient in
essential fatty acids and by evoking a primary cutaneous irritant
response by treating with a solution of sodium laurate. Impaired
barrier function was manifested by a greatly increased rate of
transepidermal water loss. Application to the skin of sunflower seed
oil, which is rich in linoleic acid, rapidly restored to normal the
abnormally high rates of transepidermal water loss in both
experimental cases, and it was shown with the essential fatty acid-
deficient rats that there was a concomitant incorporation of linoleic
acid of the sunflower seed oil into epidermal lipids. Cutaneous
application of olive oil, which is low in linoleic acid but rich in
the non-essential oleic acid, did not influence epidermal barrier
function. A close relationship of barrier function and essential fatty
acids is indicated.
PMID: 1252336

Ironically last night I got some Crazy glue on my skin, and when I
tried to peel it off, it stuck to the skin and peeled off at least one
layer of skin. The skin underneath was pink and looked like it might
bleed, but it never did, and today it's back to normal. Whatever
PUFAs I have in those cells (and the only realistic possibility is
Mead acid PUFAs), they are doing a great job !