Ingested cocoa can prevent high-fat diet-induced obesity by regulating the expression of genes for fatty acid metabolism.

[Olafur Pall Olafsson]

In the study below cocoa powder was shown to retard weight gain in
rats on a high fat diet. This was accompanied by a change in gene
expression profiles that favored the loss of mesenteric visceral fat.
Mesenteric visceral fat is particularly harmful as it drains directly
into the portal vein. What is interesting is that these effects were
found using a realistic dose of cocoa powder. The equivalent human
dose amounts to roughly 50-100g of cocoa powder daily for a 70kg
human, depending on the method one uses to calculate the equivalent
dose. I myself have been eating in excess of 50g of non alkalized
cocoa powder daily for a while. I suspect it plays a role in the
beneficial rise in my cholesterol levels which I recently reported to
the group.

Nutrition. 2005 May;21(5):594-601. Related Articles, Links
Click here to read
Ingested cocoa can prevent high-fat diet-induced obesity by
regulating the expression of genes for fatty acid metabolism.

Matsui N, Ito R, Nishimura E, Yoshikawa M, Kato M, Kamei M,
Shibata H, Matsumoto I, Abe K, Hashizume S.

Research Institute, Morinaga & Co., Ltd., Kanagawa, Japan. n-
mats...@morinaga.co.jp

OBJECTIVE: We previously found that ingested cocoa decreased
visceral adipose tissue weight in rat. To elucidate the molecular
mechanisms of that effect, we carried out experiments aimed at
analyzing biochemical parameters and gene expression profiles.
METHODS: Rats were fed either of two high-fat diets, differing only in
supplementation with real or mimetic cocoa. On day 21, body weights,
mesenteric white adipose tissue weights, and concentrations of serum
triacylglycerol were measured. To investigate the molecular mechanisms
underlying the effects of cocoa on lipid metabolism and
triacylglycerol accumulation, we examined gene expression profiles in
liver and mesenteric white adipose tissues using the GeneChip
microarray system. RESULTS: Final body weights and mesenteric white
adipose tissue weights were significantly lower in rats fed the real
cocoa diet than in those fed the mimetic cocoa diet (P<0.05), and
serum triacylglycerol concentrations tended to be lower in rats fed
the real cocoa diet (P=0.072). DNA microarray analysis showed that
cocoa ingestion suppressed the expression of genes for enzymes
involved in fatty acid synthesis in liver and white adipose tissues.
In white adipose tissue, cocoa ingestion also decreased the expression
of genes for fatty acid transport-relating molecules, whereas it
upregulated the expression of genes for uncoupling protein-2 as a
thermogenesis factor. CONCLUSIONS: Ingested cocoa can prevent high-fat
diet-induced obesity by modulating lipid metabolism, especially by
decreasing fatty acid synthesis and transport systems, and enhancement
of part of the thermogenesis mechanism in liver and white adipose
tissue.

PMID: 15850966 [PubMed - indexed for MEDLINE]

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metabolism and liver enzymes in adult rats. [J Nutr. 2000] PMID:
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Here are a few quotes from the full text article:

"Rats in the test group were maintained on an AIN-93G-based high-fat
diet containing 12.5% (w/w) cocoa powder (Pure Cocoa, Morinaga & Co.,
Ltd, Tokyo, Japan) (HC diet) and those in the control group were
maintained on essentially the same diet except for supplementation
with mimetic cocoa (HF diet) instead of real cocoa. The nutrient
contents of HC and HF diets were adjusted to be identical (Table 1),
with the mimetic cocoa made of purified major nutrients (Table 2). The
two groups of rats were pair fed on the HC or HF diet to ensure equal
energy intakes, with water provided ad libitum throughout. The amount
of cocoa intake by the rat is equivalent to 10 cups of cocoa drink (50
g of cocoa powder) per day for adult humans on the basis of energy
intake."

I think their estimation that the dose used in the study is equivalent
to 50g of cocoa powder daily for an adult human is a little low. The
rat's diet was 12.5% (w/w) cocoa powder. A person eating a 2000
calorie diet eats about 500g of food per day on a dry weight basis.
The amount of cocoa powder for a person eating a 2000 calorie diet
would then be about 500g x 0,125 = 75g of cocoa powder daily. But
extrapolating the dose is difficult since it will probably depend a
lot on the amount of polyphenols in the cocoa powder which can vary
considerably.

"As presented in Table 4 and Table 5, cocoa ingestion decreased the
hepatic gene expression for tricarboxylate (citrate) transport
protein, adenosine triphosphate citrate lyase, and fatty acid
synthase. These results indicated that cocoa decreased gene expression
of the FA synthesis system in the liver. In addition, cocoa produced
extensive decreases in the expression of genes for cholesterol
biosynthesis including squalene synthase, squalene epoxidase
(monooxygenase), and 7- dehydrocholesterol reductase (Table 4 and
Table 5."

Notice the mentioning of adenosine triphosphate citrate lyase above.
According to the full text hepatic ATP-citrate lyase levels were
downregulated almost threefold in the cocoa fed rats (which was the
strongest alteration ratio of all the genes tested in the rats
livers). I find it interesting given the fact ATP-citrate lyase is the
main target of HCA (hydroxycitric acid), a popular weight loss
supplement.

"In MES-WAT, cocoa decreased the gene expression for molecules
involved in FA transport, such as fatty acid translocase/CD36, fatty
acid transporter as a shorter form of fatty acid translocase/CD36
[26], and fatty acid binding protein (Table 4 and Table 6).
Interestingly, the gene expression for peroxisome proliferator-
activated receptor ? (PPAR-?), which is the transcription factor
inducing those FA transport-relating molecules [27], [28], [29] and
[30], was also decreased. As in the liver, cocoa ingestion similarly
decreased the expression of genes for enzymes involved in FA
synthesis, such as fatty acid synthase, 3-oxoacyl (ketoacyl)-coenzyme
A thiolase, and enoyl-coenzyme A hydratase (Table 6). It is notable
that the expression of adipocyte determination and differentiation
factor-1 (also called sterol regulatory element-1 binding protein-1c),
which is known to be the transcription factor of genes related to FA
synthesis, was also decreased [31] (Table 6). In contrast, the gene
expression of uncoupling protein (UCP) 2 as a thermogenesis factor
[32] was upregulated in HC-fed rats (Table 6). These results suggest
that cocoa ingestion leads to gene expression to decrease TG
accumulation in MES-WAT."