Trehalose Confirmed to Inhibit Fat Cell Hypertrophy

New Possibility in Metabolic Syndrome Prevention amid Global Spread of High-fat and High-calorie Diet -

OKAYAMA, Japan, September 29, 2010 - Hayashibara Biochemical Laboratories, Inc. based in Okayama City, Okayama
Prefecture, Japan, has confirmed that the naturally-derived functional
saccharide trehalose has the effect of inhibiting fat cell hypertrophy. The
finding will be presented to the 31st conference of the Japan Society for the
Study of Obesity (JASSO), scheduled to be held at Maebashi Terrsa in Gunma
Prefecture on October 1 and 2.

<< Focuses >>

- Confirmation of trehalose's effectiveness in "inhibiting fat cell
hypertrophy" and "inhibiting the progression of insulin resistance"

- Trehalose's existing use in over 20,000 types of products due to its
diverse functionality

- The latest study potentially opening a new market segment that differs
from the recently-booming market of "zero or reduced sugar/fat" products

<< Presentation overview >>

This study was conducted to identify the effects of trehalose in
preventing metabolic syndrome. Metabolic syndrome is triggered when abdominal
fat cells become hypertrophic, and induce insulin resistance. The study
involved tests on mice that were fed a high-fat diet (HFD) and given a range
of saccharides for comparison. The results showed that trehalose can
effectively inhibit the hypertrophy of fat cells, which usually occurs in
HFD. Furthermore, the saccharide was found to inhibit the progression of
insulin resistance, normally triggered by HFD. The findings point to the
possibility of developing a new approach to prevent metabolic syndrome while
consuming necessary saccharides.

<< Significance of this study >>

Today, Japanese people are increasingly embracing the Western-style
high-fat and high-calorie diet. Consequently, the proportion of people with
obesity resulting from excessive intake of fat and sugar has increased over
the last decade, especially among middle-aged and senior citizens. In recent
years, the food market has seen a surge of products with "zero or reduced"
calories, sugar and fat amidst strong support from consumers.

However, saccharides are one of the essential nutrients required to
sustain life, serving various beneficial roles in our bodies. For example,
saccharides (glucose) are the source of energy for our brain. Its deficiency
causes performance deterioration and emotional instability. When the brain
does not feel satisfied as in a saccharide-deficient diet, it interprets the
situation as a state of starvation, and triggers excessive eating to
supplement energy, thereby causing eating disorders.

Trehalose is turned into glucose by our bodies and serves a vital role as
a vital nutrient. In carrying out a study focused on the already-proven
effect trehalose had in evoking lower insulin secretion, it was identified in
this study that trehalose inhibits the hypertrophy of fat cells.

In other words, this study presents an extremely novel possibility that
"saccharides," which previously carried a "fattening" image, can become a
tasty alternative to "zero/reduced" products as a kinder way of preventing
metabolic syndrome.

<< Research overview >>

Objectives

In order to examine trehalose's effectiveness in preventing metabolic
syndrome, mice on a high-fat diet (HFD) were given trehalose and other
saccharides for comparison to gauge its effect on fat cell hypertrophy, as
well as other saccharides for comparison.

Testing method

Seven-week-old mice were divided into seven groups: one on a normal diet
and water; one on HFD and water; and five on HFD and various saccharide
solutions (trehalose, etc.). They were kept on their respective diets for
eight weeks. The mice were then subjected to a glucose tolerance test in Week
7, and had the diameter and area of their visceral fat (mesenteric fat cells)
measured in Week 8, in order to determine the effect of trehalose in
inhibiting the hypertrophy of fat cells.

       [Grouping of samples]

    A. Normal Group:         Group on normal diet + water
    B. Control Group:        Group on HFD + water
    C. Trehalose Group:      Group on HFD + trehalose
    D. Glucose Group:        Group on HFD + glucose
    E. HFCS Group:           Group on HFD + high fructose corn syrup (HFCS)
    F. Fructose Group:       Group on HFD + fructose
    G. Maltose Group:        Group on HFD + maltose
           * Each saccharide was given in the form of a 2.5% solution.

    Measurement items
    1) Diameter and area of mesenteric fat cells
    2) Fasting blood sugar/insulin levels

Results

Microscopic photography was taken on visceral fat samples from all groups
in Week 8 to compare the extent of their hypertrophy. Group B on HFD showed
hypertrophy of mesenteric fat cells compared to Group A on ordinary diet (fat
cell diameter: 40-50 micrometer in Group A [normal group] and 80-90
micrometer in Group B [control group]). Growth in fat cell size for Group C,
which was given trehalose solution to drink, was inhibited (fat cell
diameter: 60-70 micrometer). No such inhibition was demonstrated in Groups on
other types of saccharide (fat cell diameter: 85-100 micrometer in Group D,
80-90 micrometer in Group E, 80-90 micrometer for Group F, and 85-100 for
Group G).

As for mesenteric fat cell area, Group G on HFD had a larger per-cell
area than Group A on ordinary diet. Area increase for fat cells of Group C on
trehalose was inhibited, while Groups on other saccharide (Group D, Group E,
Group F and Group G) had greater per-cell area than Group B.

*For the measurement of mesenteric fat cells, an optical microscope (at
200x magnification) was used to take a photograph of five randomly-selected
fields. The number of fat cells per microscopic view (0.267mm2) was counted
to work out the per-cell area.

Sample fasting serum insulin and insulin resistance were examined in Week
7. Compared to Group A on ordinary diet, Group B on HFD showed a raised level
of fasting blood sugar and fasting serum insulin, as well as insulin
resistance index (HOMA-IR), which is calculated with the two figures.
Meanwhile, increase in fasting serum insulin for Group C, which was trehalose
solution, was inhibited. This, in turn, lowered the HOMA-IR index to indicate
improvement in insulin resistance. This effect was not observed in groups on
other saccharides (Group D, Group E, Group F and Group G).

*This study has also confirmed trehalose's effectiveness in inhibiting
the progression of glucose tolerance impairment and protecting pancreatic
beta cells, which secrete insulin.

<< Future potential >>

The main achievement of this study is the discovery that saccharides,
which are usually associated with weight gain, inhibit the fat cell
hypertrophy that causes metabolic syndrome. This insight should be further
explored to identify the mechanism of fat cell hypertrophy inhibition, and
examine whether the same effect is obtained in humans. Human verification
tests are planned to examine the saccharide's effect of inhibiting
progression of pre-metabolic syndrome. Hayashibara Biochemical Laboratories
is committed to further research to advocate more effective use of trehalose
in preventing metabolic syndrome.

*A detailed news release featuring graphs and images showing research
results is available on the Hayashibara website, which can be visited at the
following URL: www.hayashibara.co.jp/english/index.html

    Contact:  Staff in charge: Mika Kimura (c/o Ozma Inc.)
              Tel: +81-3-3403-0581
              Fax: +81-3-3403-0289
              E-mail: treha@ozma.co.jp

Mika Kimura of Ozma Inc., +81-3-3403-0581, fax, +81-3-3403-0289, treha at ozma.co.jp, for Hayashibara Biochemical Laboratories, Inc.