HEALTH AND NUTRITION NEWSNo. 6
December 15, 2003 volume 2 number 3

Table of Contents
PREFATORY NOTEExpectation to the National Institute of Health and Nutrition …………....…….……Yoshiko KAGAWA
CURRENT RESEARCH PROJECTS
Diet and Energy Expenditure ……………………………………………...….………Toshimasa OSAKATHOUGHTS ON HEALTH AND NUTRITION RESEARCH
From Index Medicus to Medline: Changes in the method for searching medical research
articles and outlook for a research institute ……………………………….….…………Satoshi SASAKIRESEARCH FINDINGSAre there oils really preventing for fat deposition in the body?

.………..…...Nobuko TSUBOYAMAHesperidin, a citrus flavonoid, inhibits bone loss and decreases serum and hepatic lipids inovariectomized mice ………………………………………………...…………………..….Yoshiko ISHIMI
Association of peroxisome proliferators-activated receptor γ coactivator-1 α (PGC-1α) toexpedite glucose metabolism induced by physical activity ……………………..…………Shinji MIURA© National Institute of Health and Nutrition

Prefatory NoteExpectation to the National Institute of Health and Nutrition
Dr. Yoshiko Kagawa (President of Kagawa Nutrition University)

I have been a member of external
evaluation committee for last two years since theNIHN became an incorporated administrative
agency. Not surprisingly, facilities and staff are
outstanding as expected of being a pioneer in thefield of nutrition in Japan.
First of all, their primary research area is
on basic human nutrition such as a nutrient and its
metabolism, and nutri-genomics. The study ofenergy metabolism is one of core research areas
since the NIHN was found, but it has been
upgraded with the new technology. This area isvery important to study because many of Japaneseare now facing with the problem of consuming too
much energy. The study of nutrition is not limited in
the basic research, but a research to enhance thepublic health is well demanded. “Evidence-basedNutrition” (EBN), a study of nutrition based on ascientific evidence, should be at the base. EBN
often requires researches on human, so that it ismore difficult to conduct compared to an animalstudy. For instance in the study of gene,
researchers are eager to develop an order-madenutritional advice based on one’s physiologicalconstitute in future.
On the other hand, the number of people
who is not concerned their diet is increasing due tothe change in society, food environment, andfamily structures. The “National Nutrition Survey”(now changed its name to the National Health andNutrition Survey) has been providing reliable data
concerning the diet of the Japanese every year
since 1946, and this survey is now further
upgraded with the extended sample size andcontent. I look forward NIHN to make further efforts
to progress in order to obtain enhanced data.
In addition, people who are either lessconcerned their diet or eating unbalanced diethave been more dependant on dietary
supplements, and there are more demands by thepublic for information on functional foods, BSE,
pesticides, genetically modified foods, and false
food labeling. Therefore, studies on cooking areinevitable. NIHN has worked on these various
areas to meet large expectations from the public.
It is always said that an individual-based
nutrition education is important. However, if one
does not follow the advice, it is putting the cart
before the horse. Yet, it always happens. We havechanged the food we eat, so that we need
instructions on how to eat. A study of foodpreference and psychological issues behind dietshould be also looked before implementing aneducation
Japan has the longest life expectancy inthe world. On the other hand, the number of people
who suffers from lifestyle-related diseases such as
diabetes and obesity is also increasing. One of thereasons is lack of physical activity. The study ofnutrition and/or physical activity will have a great
impact on one’s health and wellbeing in long run.
Therefore, we need more data to make a policy.
“Health Improvement Law” was enacted last year,and people are now responsible for improvement
and maintenance of own heath status. In addition,
almost of all target areas in “Health Japan 21” haveincluded nutrition-related topics. The publicawareness will continuously increase, so that
NIHN should make continuous efforts not only tomake great accomplishments in the field ofnutritional research, but also to provide valuable
information to the public.

2Current Research Projects
Diet and energy expenditure
Dr. Toshimasa Osaka (Senior Researcher of Division of Human Nutrition)

Many of you may have experienced thesensation of warmness after eating pot-stew ormeals cooked with chili peppers. On the other
hand, some may have sweated while you ate
meals in hot summer. This is not simply caused
by ingestion of hot meals, but rather the heat is
induced as a result of the energy synthesis ofnutrients during or after the digestion of meals.
This type of energy expenditure has been known
as “dietary induced thermogenesis.” This takes up
to 10% of the total energy intake, and it is takenplace in everyone, even for those who do not
exercise regularly. Therefore, although it might bethought to be only a little, but this would affectone’s body weight in long-run.
No one consistently consume the sameamount of calories everyday, but why one’s bodyweight relatively stays the same? The reason isthat the body not only regulates the energy intake,but also regulates the expenditure to keep thebalance. “Obesity” is caused when the energy
intake exceeds the expenditure, and that willfurther lead other lifestyle-related diseases suchas diabetes, hypertension, and hyperlipidemia, as
many of you have already known. Therefore, if wecould control the energy expenditure, it would
effectively prevent developing lifestyle-relateddiseases. However, how the body regulates theenergy expenditure is still unknown.
“Dietary induced thermogenesis” is theenergy derived from digestion of foods we eat, as
well as from absorption, metabolism, and storageof nutrients. In addition, food satiety or chewing
will increase the energy expenditure. In addition,
we now know that the brain is involved in thisregulatory system due to our sense of taste orsmell, and our expectation to or experiences withmeals. We are currently studying about the basic
physiology how food components or hormones
secreted for energy metabolism by digestivesystems due to ingestion of such foods.
The energy expenditure is mostly
regulated by the autonomic nervous system(vagal nerve and sympathetic nerve). For
instance, the vagal nerve detects an ingested ordigested food component at first, and thentransmits a signal to the brain, which then will
send an order to the sympathetic nervous system
to regulate the energy expenditure. The signal
sent to the brain will also influence a food intake.
Those food components and hormones will act as“satiety substance” on brain to generate thesense of fullness and to increase the energy
expenditure. Overall, it will prevent an
accumulation of excess energy in the body. The
brain regulates this system, and usually it isunconsciously taken place in the body. If
something happens to this mechanism, it may
lead to obesity. Our future plan is to clarify how
signals from digestive system are sent to thenervous system or brain, how energy metabolism
or the sense of fullness is regulated, and whichpart of the brain is involved in this work.

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Thoughts on Health and Nutrition Research
From Index Medicus to Medline: Changes in the method for searching medical
research articles and outlook for a research institute
Dr. Satoshi Sasaki (Head of Dietary Reference Intakes)
A decade ago, we referred to “Index

Medline is accessible by anyone. It may

Medicus”, a high volume book listed only titles ofneed some techniques at first time, but I strongly

articles, in order to look for medical research

recommend trying out at least once. For instance,articles. Therefore, we used to spend hours in thetype “Sasaki S” AND (intake OR consumption OR

library to look for the article we wanted. Even after

diet OR dietary) in the search box, and hit an

we found the title, we still had to transcribe theenter key. This allows knowing how many articles

name of the journal, year, volume, and pages.

“Sasaki S” has published or what area of interests

Then we searched shelves or had to ask

he has. However, if more than one “Sasaki S”

librarians to order copies by interlibrary loan ifexist (mostly in this case, “yes”), it is difficult tothey did not have it. In many cases, however, wedetect the right one. In addition, if his area of

realized that it was missing out the content weinterest is on variety topics, you need to put morewanted after reading the whole article. The

keywords and connect with “OR”. If the number ofUniversity of Ruben in Belgium is the world oldest

hit articles was not many enough as you expected,

catholic university found in 1425, and has athere would be two possible reasons: one is “notcollection of medical journals published worldwide.

publishing enough” and the other is “incorrect

Through years while I was a doctorate student atsearch keywords.” Furthermore, there are many

that university, I was allowed to use their

medical journals not listed in Medline, so that thisresources freely, and was able to enhance myis one out of many ways to have rough ideas.

knowledge and intelligence.

After going through such trials, youHowever, few years later, the National

might understand that Medline is very useful tool

Library of Medicine in the United States started

but requires some techniques and expertise. In

providingcalledaddition, since we can only get access to a“Medline” through an internet. Soon after, thesummary on Medline, we still need to rely on aservice became free of charges. Even at home,library to read whole papers. Information-driven

we can now access to this database, whichsociety would also apply to research areas. An

contains over 9,000,000 articles, to search andeffective utilization of resources such as Medline

even to read summary of an article. Previously,

and appropriate library facilities to support it are

we had spent a month at a library, but now it only

two keys to determine whether Japan cantakes an hour in order to get the same outcome.

successfully become an intelligent producing

This information infrastructure has contributed asociety to produce a high level of research

lot to researchers. Furthermore, such intellectualoutcomes. For these times, I remember good oldproperties, only available for limited number ofdays in the Ruben university library.

medicalarticledatabase

people at research institutes or universities inone-time, are now open to everyone in the world.

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Research Findings
Are there oils really preventing for fat deposition in the body?
Dr. Nobuyo Kasaoka-Tsuboyama (Researcher of Division of Clinical Nutrition)
In recent days, we see various types ofweredeveloped(1.3gCLA/kg

body

weight;fats and oils in supermarkets, and especiallyapproximately 70 times more than normallythose claiming for “preventing fat deposition in thecontained in dietary supplements). When feedingbody” are drawing attention. These types of oils

smaller amounts of CLA (0.13gCLA/kg bodyare sold not only as cooking oil, but also asweight; approximately 7 times more than normally

dietary supplements. Quite a lot of people havecontained in dietary supplements), body fat was

doubted the consequence, but is that really so?

reduced without causing any adverse effect. In

Fats are made of “fatty acids”, and aconsequence, we found that feeding small

number of fatty acids exist in nature. Some ofamounts of CLA is necessary to control obesity. In

those are indispensable for life, but others are not,addition, even if someone ever consumes larger

even though those still provide some functions toamounts of CLA than safe levels, we can still

the body. Some fats are less likely to accumulate

avoid developing fatty liver and/or diabetes byin the body, and these types of fats are used foreating high-fat diet. This suggests that it is better

manufacturing“oilsto add CLA to edible oils, rather than to dietarydeposition.”

However, some products arepreventingbodyfat

supplements, in order to prevent obesity.

enriched with a fatty acid which barely presents inIn addition, after we studied how CLA

nature, or others contain a fatty acid whose

had caused fatty liver, we found that CLA directly

chemical structure was slightly changed from theworked on genes involved in the fat synthesis

ordinal one. Furthermore, some products are not(SREBP-1 and its targeted gene) to enhance theclearly confirmed to have a property declared, orformation of fatty liver.

whether those are safe enough to consume. We

In this study, we fed 7 to 70 times of CLA

have been studying to evaluate whether thesemorefatty acids truly have such declared properties orsupplements. Therefore, eating regular meals

how much we should consume, and if there arewould not cause a health problem. However, if

any adverse effect or not.

you take some nutrients like CLA that regulatethannormallycontained

indietary

We used a conjugated linoleic acidany particular gene, you should be concerned.

(CLA), a fatty acid often found in meats and dairy

Those fats and oils declared for “preventing fatproducts, and we found that the fat mass ofdeposition” might work differently, but still fats are

CLA-fed mice was significantly reduced. Bothessential to maintain our physiological function.

visceral and subcutaneous fats were reduced as

Therefore, we need to be careful to avoid

levels of CLA increased, so that we concluded

excessive depletion of body fat stores at any time.

that CLA has a positive effect on obesity control.
Reference: Increasing the amount of fat in a
conjugated linoleic acid-supplemented diet
reduces lipodystrophy in mice. TsuboyamaKasaoka N, Miyazaki H, Kasaoka S, Ezaki O: JNutr.: 133:1793-99, 2003On the other hand, feeding too much CLA led
extreme reduction of body fat, even thoseessential to maintain the physiological function,and further conditions like fatty liver and diabetes
5Research Findings

Hesperidin, a citrus flavonoid, inhibits bone loss and decreases serum and hepatic
lipids in ovariectomized mice
Dr. Yoshiko Ishimi (Chief of Laboratory of Assessment of Food Function)

The article reported that the synthesis ofresult,hesperidin,

acitrusflavonoidcholesterol was reduced in statin-fed rats, in thepredominantly found in an orange peel, inhibited

American journal called “SICENCE” 4 years ago.

bone loss and decreased serum and hepaticThis finding had a great impact around the world,lipids in ovariectomized mice. The peel ofand many case-control studies were conducted“Satsuma mandarins” contains large amounts ofregarding the relationship between the use ofhesperidin, but we further need to analyze if thestatin and bone mass. As a result, many studies

same mechanism would occur in human. The

have reported that the incidence of hip bonepeel of oranges has been popular in Chinesefracture was lower in statin-taking menopausal

medicines as “Chinpi” to maintain the health ofwomen and elderly people, compared to thosethe digestive system and to relieve cough. Why

who did not. The trial was also conducted in

do not you try marmalade for breakfast?

Japan with middle-aged women, and increasedbone density was observed in those taking statin.

Reference: Chiba H, Uehara M, Wu J, Wang X,

nutritional

Masuyama R, Suzuki K, Kanazawa K, Ishimi Y.

researches to prevent osteoporosis. Recently, weHesperidin, a citrus flavonoid, inhibits bone loss

have looked at a citrus flavonoid, which wasand decreases serum and hepatic lipids inthought to have a capacity to lower the synthesis

ovariectomized mice. J Nutr. 133: 1892-1897,of cholesterol, in relation to bone turnover. As a2003.

We

haveconducted6

Research Findings
Association of peroxisome proliferators-activated receptor γ coactivator-1α(PGC-1α) to expedite glucose metabolism induced by physical activity
Dr. Shinji Miura (Researcher of Division of Clinical Nutrition)
After engaged in prolonged exercise,body fat is burned due to the increased number ofmitochondria in skeletal muscles, and the glucose
metabolism is activated by the increased numberof glucose transporter (GLUT4) to take blood
glucose in skeletal muscles. Regular exercise isthought to prevent developing lifestyle-relateddiseases like diabetes, and the above mechanismof skeletal muscles is thought to explain it.
Recently,
peroxisome
proliferatorsactivated receptor γcoactivator-1α(PGC-1α), a
substance regulating genetic transcription, wasfound to expedite the synthesis of mitochondria.
In addition, the study of cultivating skeletal
muscle cells has reported that PGC-1αhad
increased the number of GLUT4 in skeletal
muscles. PGC-1αalso presents in skeletal
muscles and we have observed that the number
was increased after exercise. According to theseresults, we have concluded that the change in thestructure of skeletal muscles is due to theincreased number of PGC-1αinduced byexercise.
In this study, we used transgenic micewith the elevated level of PGC-1αonly in skeletal
muscles in order to examine whether or not theincreased number of mitochondria and GLUT4 by
exercise is as a result of the increased number of
PGC-1α, in vivo (figure 1).

and the activation of glucose metabolism (figure2).

Figure 2
In future, some diabetes medications
targeting PGC-1αmay be introduced, but too
much PGC-1αmay cause adverse effects such as
glucose intolerance. Therefore, we eager to find a
GLUT4 enhancing substances, other than
PGC-1α, to avoid any possible side effect.
1)

Glucose Intolerance: Insulin is secreted frompancreas after ingestion of meals to take blood
glucose in skeletal muscles via GLUT4, so thatblood glucose is kept within the normal level.
However, in people with glucose intolerance,
insulin is secreted normally but blood glucose is
not taken up by skeletal muscles due toinactivated GLUT4. Accordingly, insulin no longer
regulates blood glucose level, and this would
result in high blood sugar level. Eating too muchfood (especially high-fat diet) and sedentary
lifestyle are thought to be reasons for developing
glucose intolerance. This is a precursor for type 2

Figure 1
In
PGC-1α-transgenic
mice,
weobserved the increased number of mitochondriaand red muscles (muscles appropriate forprolonged exercise like marathon), but the level of
GLUT4 expression was lowered. In addition,
glucose intolerance1) was also observed. In
conclusion, the number of mitochondria will
increase with increasing the number of PGC-1αinskeletal muscles over a long period of time, but it
is not associated with overexpression of GLUT4

diseases in Japan.
Reference: Overexpression of peroxisome
proliferator-activated receptor γ coactivator-1α(PGC-1α) down-regulates GLUT4 mRNA in
skeletal muscles. Miura S, Kai Y, Ono M, Ezaki O:
J Biol Chem.: 278(33):31385-31390, 2003.

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