Study shows how to prevent a high-fat diet from throwing metabolism out
of whack
Biologists discover removing a protein inhibitor restores metabolic
balance

Date:
April 5, 2023
Source:
University of California - Irvine
Summary:
Eating lots of fats increases the risk of metabolic disorders,
but the mechanisms behind the problem have not been well
understood. Now, biologists have made a key finding about how to
ward off harmful effects caused by a high-fat diet.


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FULL STORY ========================================================================== Eating lots of fats increases the risk of metabolic disorders, but
the mechanisms behind the problem have not been well understood. Now, University of California, Irvine biologists have made a key finding
about how to ward off harmful effects caused by a high-fat diet. Their
study appears in Nature Communications.


==========================================================================
The UC Irvine research centered on a protein complex called AMPK, which
senses the body's nutrition and takes action to keep it balanced. For
example, if AMPK detects that glucose is low, it can boost lipid breakdown
to produce energy in its place. Scientists have known that consuming
high amounts of fat blocks AMPK's activity, leading the metabolism to
go out of balance. However, until now, how cells block this mechanism
has not been widely examined, especially in live models.

The UCI biologists decided to investigate, believing an AMPK component
called SAPS3 serves a significant role. They eliminated SAPS3 from
the genome of a group of mice and fed them meals with a 45 percent fat
content. The results were startling even to the research team.

"Removing the SAPS3-inhibiting component freed the AMPK in these mice
to activate, allowing them to maintain a normal energy balance despite
eating a large amount of fat," said Mei Kong, professor of molecular
biology & biochemistry and the study's corresponding author. "We were
surprised by how well they maintained normal weight, avoiding obesity
and development of diabetes." The discovery could eventually lead to
a new way to approach metabolism-related conditions. "If we block this inhibition activity, we could help people reactivate their AMPK," said
first author Ying Yang, a project scientist in the Kong lab. "It could
help in overcoming disorders such as obesity, diabetes, fatty liver
disease and others. It's important to recognize how important normal
metabolic function is for every aspect of the body." The researchers
are working on developing molecules that could inhibit SAPS3 and restore
the metabolism's balance. They plan to next study SAPS3's role in other conditions with disturbed metabolic systems, such as cancer and aging.

The discovery comes as metabolic-related diseases such as obesity and
diabetes continue to rise. More than half of the global population is
expected to be overweight or obese by 2035, compared to 38 percent in
2020, according to the World Obesity Federation. The number of people
worldwide with diabetes is expected to rise to 578 million by 2030,
up 25 percent from 2019, reports the National Center for Biotechnology Information.

Support for the project was provided by the National Institutes of Health
and the American Cancer Society.

* RELATED_TOPICS
o Health_&_Medicine
# Obesity # Diet_and_Weight_Loss # Fitness # Nutrition
# Diabetes # Cholesterol # Diseases_and_Conditions #
Chronic_Illness
* RELATED_TERMS
o Atkins_Diet o Trans_fat o South_Beach_diet o Diabetic_diet
o Healthy_diet o Eating_disorder o Zone_diet o Unsaturated_fat

========================================================================== Story Source: Materials provided by
University_of_California_-_Irvine. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Ying Yang, Michael A. Reid, Eric A. Hanse, Haiqing Li, Yuanding
Li, Bryan
I. Ruiz, Qi Fan, Mei Kong. SAPS3 subunit of protein phosphatase
6 is an AMPK inhibitor and controls metabolic homeostasis upon
dietary challenge in male mice. Nature Communications, 2023; 14
(1) DOI: 10.1038/s41467- 023-36809-1 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/04/230405161412.htm

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