> ... people produce buckets of it. [of stearic acid. roro]
Don,
they do. But something eats it up at once. This something is called
StearoylCoA-Desaturase (SCD-1) and transforms a supposedly bad guy
(saturated stearic acid, SA) into a good one ('mediterranean' oleic acid,
OA). Did you ever think about why the adipose tissue of starch-fed animals
like pigs (and of many humans) contains a lot of OA, much palmitic acid and
only small amounts of SA?
In mammals, OA synthesis is performed in three steps. An enzyme complex
called fatty acid synthase (FAS) at first makes a palmitic acid from carbs
or amino acids as primary source. It stops at a chain length of 16 carbons.
The
n a separate enzyme, Long Chain Elongase [1] (LCE), adds two more carbons
resulting in SA. And, finally,a cis-doublebond is inserted in the middle by
SCD-1. Therefore, the lots of OAs in adipose tissue of animals with
negligible fat intake have to pass the SA-step. The relative activities of
LCE and SCD-1 are critical for the SA-content not only of the fat cells but
of cell membranes, too. The group of James Ntambi in Madison, WI, worked
more than 15 y about the SCD-1 enzyme [2] and found out some strange
properties.
First, the SCD-1 product OA has well known indispensable metabolic functions
similar to it's precursor SA. Virtually every cell is able to synthesize
them and thus they cannot be essential in the strict meaning, of course. A
loss of this capability would most likely make us die before birth. But in
spite of being one of the most abundant nutrients, OA from the meals or just
from our stores
cannot be reused in some metabolic processes like
lipoprotein assembly [3] and cholesterol/wax-ester formation [4]. It has to
be built de novo by SCD-1 from SA! This makes SCD-1 an extremely important
control point of our metabolism and results in a continuous need for SA. And
that's not all. SCD-1 knockout mice don't get fat even if they are fed a
fatty chow. This is not because they eat less. They burn more fat [2,5,6]!
This canonly be explained in two ways. Wherever the metabolic target may be,
either the diminished availability of SA or the formation of an OA-compound
makes mice fat. It was made probable [2,5] that one of these targets is the
combustion control of the mitochondria in muscle, liver, and other organs.
SA stimulates the fat combustion maximally if compared to other fatty acids
and SCD-1 attenuates burning by transforming it locally into the less
activating OA and by supporting fatty acid
synthesis [7,8,9]. This makes
much sense! SCD-1 is one of the most strongly induced enzymes in lipogenic
states [10], something many people don't like very much to be in and that
should not be present in a paleodiet. In such a state,it seemsmetabolically
reasonable to spare fats by lowering their combustion first before starting
their production. If the burning of energy has to be sustained, cells could
directly burn the carbs.
But there is one situation where these mechanisms have to be overridden: if
there is a lack in metabolically needed SA. As the two SA-forming
enzymes FAS and especially the rate limiting LCE [11] (that apparently can
use external or stored palmitic acid) both are lipogenic enzymes [10], a
lipogenic state has to be induced whatever the nutritional status may
be. Even on a weight reduction diet. A diet rich in fat but low in SA will
result in fuelling of dietary fat into our st
ores and additional SA/OA
production. If SA supply is low, a diet rich in carbs might even be better
because the body has only to produce as much fat as is needed for the
mentioned metabolic processes.
But in a non-lipogenic fatty diet, SA becomes really somehow essential.
There are classical studies showing the nutritional advantages of SA
[12,13]. Obese or insulin resistant people have high blood levels of fatty
acids. Why shouldn't our liver and muscles be able to use an abundant fat
supply from the stores for lipoprotein production or heating [14],
respectively, like at the time when we lost our fur? If we consider the
papers [2], [5], and [20], an obvious explanation would be a wrong
composition of the fatty acid stream from adipose tissue. Indeed, low SA
content of our fat cells (and cell membranes) was identified as a risc
factor(s) [15].
A low SCD-1 activity st
rongly enhances insulin sensitivity [16]. So an
important process could be the induction of a vitious cycle: Low SA supply
would cause insulin resistance to induce a lipogenic state by increase of
insulin production and thus to rise the SA-production. But as SCD-1 is the
most strongly induced lipogenic enzyme [10], the situation could become even
worse because of enhanced SA-desaturation. Especially the intake of fructose
containing sugars could be deleterious as fructose directly induces
additional SCD-1 [19] without involving the insulin-axis.
A diet rich in fructose/fat and poor in SA seems to be ideal to get fat.
Additionally is there evidence that one metabolic SA-sensor is a so called
orphan receptor named HNF4alpha [17,18]. If this receptor has a mutation in
its lipid recognizing domain, an inheritable form of diabetes occurs [18].
One can imagine what happens if the natural ligand of HNF4a is
lacking.
HNF4a seems even to be involved in the important metabolic switch mechanisms
acting during weaning. As human milk fat is low and the fat of grass fed
ruminants (and elephants/mammoths, glacial adult food) is
rich in SA from their gut bacteria one can construct a path from the fat
type consumed to the fine tuning of the metabolic point of work. But that is
another story.
Fats can be categorized in four groups in respect to their SA content.
(i) Most vegetable oils and fats are very low in SA.
(ii) A few have very high SA contents (30-40%) but they are exotic or
expensive: shea butter, cupu assu and cocoa butter.
(Be aware of the fructose/saccharose [19] in black chocolate!).
(iii) Fats of non-ruminants, especially carb-fed, contain around 10%, like
milk fat of cows. The milk fats of other animals (camels? buffalos?)
possibly contain more.
(iv)
Fat depots of ruminants contain around 20%. Thus a paleolithic diet
with 60-70% fat should have supplied at least 12-14 kcal% SA.
I must admit that the quoted arguments are no definitive proofs. But most of
the cited papers are not that kind of greasy woodoo but rock solid biochemistry.
Roland
[1] Moon YA, et. al.
Identification of a mammalian long chain fatty acyl elongase regulated by
sterol regulatory element-binding proteins.
J Biol Chem 2001 Nov 30;276(48):45358-66.
[2] Ntambi, JM, et. al.
Recent insights into stearoyl-CoA desaturase-1.
Curr Opin Lipidol 2003 Jun;14(3):255-61.
[3] Miyazaki, M, et. al.
A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase-1
gene reveals a stringent requirement of endogenous monounsaturated fatty
acids for triglyceride synthesis.
J Lipid Res 2001 Jul;42(7):1018-24.
[4] Miyazaki C M, et. al.
Targeted disruption of stearoyl-CoA desaturase1 gene in mice causes atrophy
of sebaceous and meibomian glands and depletion of wax esters in the eyelid.
J Nutr 2001 Sep;131(9):2260-8.
[5] Cohen, Paul
Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss.
Science 2002 Jul 12;297(5579):240-3.
[6] Ntambi JM, et. al.
Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity.
Proc Natl Acad Sci U S A 2002 Aug 20;99(17):11482-6.
[7] Lunzer, MA, et. al.
Inhibition of rat liver acetyl coenzyme A carboxylase by long chain acyl
coenzyme A and fatty acid. Modulation by fatty acid-binding protein.
J Biol Chem 1977 Aug 10;252(15):5483-7.
[8] McGee, R, et. al.
Fatty acid biosynthesis in Erlich cells. The mechanism of short term control
by exogenous free fatty acids.
J Biol Chem 1975 Jul 25;250(14):5419-2
5.
[9] Goodridge, AG, et. al.
Regulation of fatty acid synthesis in isolated hepatocytes prepared from the
livers of neonatal chicks.
J Biol Chem 1973 Mar 25;248(6):1924-31.
[10] Horton, JD, et. al.
Combined analysis of oligonucleotide microarray data from transgenic and
knockout mice identifies direct SREBP target genes.
Proc Natl Acad Sci U S A 2003 Sep 25;.
[11] Marcelo, CL, et. al.
Fatty acid metabolism studies of human epidermal cell cultures.
J Lipid Res 1993 Dec;34(12):2077-90.
[12] Bonanome, A
Effect of dietary stearic acid on plasma cholesterol and lipoprotein levels.
N Engl J Med 1988 May 12;318(19):1244-8.
[13] Newbold HL
Reducing the serum cholesterol level with a diet high in animal fat.
South Med J 1988 Jan;81(1):61-3.
[14] Bavenholm, PN, et. al.
Insulin resistance in type 2 diabetes: assoc
iation with truncal obesity,
impaired fitness, and atypical malonyl coenzyme A regulation.
J Clin Endocrinol Metab 2003 Jan;88(1):82-7.
[15] Yli-Jama, P, et. al.
Serum free fatty acid pattern and risk of myocardial infarction: a
case-control study.
J Intern Med 2002 Jan;251(1):19-28.
[16] Rahman, SM, et. al.
Stearoyl-CoA desaturase 1 deficiency elevates insulin-signaling components
and down-regulates protein-tyrosine phosphatase 1B in muscle.
Proc Natl Acad Sci U S A 2003 Sep 16;100(19):11110-5.
[17] Navas, MA, et. al.
Functional characterization of the MODY1 gene mutations HNF4(R127W),
HNF4(V255M), and HNF4(E276Q).
Diabetes 1999 Jul;48(7):1459-65.
[18] Dhe-Paganon, S, et. al.
Crystal structure of the HNF4 alpha ligand binding domain in complex with
endogenous fatty acid ligand.
J Biol Chem 2002 Oct 11;277(41
):37973-6.
[19] Waters, KM, et. al.
Insulin and dietary fructose induce stearoyl-CoA desaturase 1 gene
expression of diabetic mice.
J Biol Chem 1994 Nov 4;269(44):27773-7.
[20] Jen, KL, et. al.
Differential effects of fatty acids and exercise on body weight regulation
and metabolism in female Wistar rats.
Exp Biol Med (Maywood) 2003 Jul;228(7):843-9.
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