Exercise during pregnancy reduces the risk of Type-2 Diabetes in
offspring

Date:
April 14, 2022
Source:
Tohoku University
Summary:
Exercising during pregnancy bestows a wealth of benefits upon
a child.

New research suggests that exercise may also help reduce the
offspring's chances of getting type 2 diabetes. Researchers
uncovered how SOD3, a key protein released by the placenta after
exercise, improves the metabolic health of offspring and negates
the impacts of maternal obesity and poor diets.



FULL STORY ==========================================================================
A new study has demonstrated that maternal exercise during pregnancy
improves the metabolic health of offspring, even when the mother is
obese or on a high- fat diet. Physical exercise by the mother induces
the placenta to secrete the key protein SOD3, resulting in a lowered
risk of diabetes for the offspring.

The findings in the paper identified the mechanisms behind this process.


==========================================================================
The results were published in the Journal Diabeteson March 15, 2022.

A worrying trend Maternal obesity and type 2 diabetes are on the
rise. Over 30% of women of childbearing age in Western and Asian countries
are classified as obese.

Meanwhile, 630 million people are expected to be living with type 2
diabetes by 2045. Children born to obese mothers or mothers with type
2 diabetes have an increased risk of diabetes, even after going on to
live healthy lives.

"With the growth of maternal obesity, a worrying cycle is forming
where the risks of diabetes gets passed down from generation to
generation," says assistant professor Joji Kusuyama from Tohoku
University's Interdisciplinary Institute for Frontier Sciences (FRIS),
and lead author of the study. "Stopping this cycle is a critical and
pressing medical problem." In the research group with Kusuyama was
Laurie Goodyear, Nathan Makarewicz, Brent Albertson, Ana Alves-Wagner,
Royce Conlin, Noah Prince, Christiano Alves, Krithika Ramachandran,
and Michael Hirshman from the Joslin Diabetes Center; Chisayo Kozuka
from RIKEN's Center for Integrative Medical Sciences; Toshihisa Hatta
from Kanazawa's Medical University; Yang Xiudong and Yang Xia from
the University of Texas at Houston; and Ryoichi Nagatomi from Tohoku University's Graduate School of Biomedical Engineering.



========================================================================== Previously, the group showed that exercise during pregnancy has
tremendous benefits on an offspring's metabolic health, demonstrating
that placenta- derived SOD3, which stands for supuroexide dismutase 3,
plays a key role in transmitting the benefits of maternal exercise to
the offspring. Building on this, the team set out to understand how SOD3 prevents the negative effects of obesity being passed from mother to
child and found that SOD3 inhibited high- fat diet-induced abnormalities
in the offspring's glucose metabolism.

The link between maternal and childhood obesity Histone methylation plays
a fundamental role in epigenetic modification - - heritable changes to
strands of DNA that do not affect the inherited base pairs. Methyl group
(-CH3) attaches to an amino acid in the tail of histone proteins that
wrap DNA, sometimes activating gene expression, sometimes inhibiting it.

When a mother consumes a diet heavy in fat, the histone H3 trimethylation H3K4me3 gets decreased in the fetal liver and hinders the expression of
glucose metabolism genes.

This, the researchers discovered, is caused by two things. Reactive
oxygen species (ROS) -- oxygen in a reactivated and activated state
which aids the body's metabolism and cellular functions -- becomes
elevated. Meanwhile, WDR82, a key protein that regulates histone methyltransferase, becomes oxidative, impairing protein functions.



==========================================================================
The harmful effects of a maternal high-fat diet on an offspring's
metabolism are reversed by maternal exercise. Genetic manipulation
demonstrated that placental SOD3 is indispensable for the protective
effects of maternal exercise on offspring.

The study also highlighted how crucial exercise is for negating this. When
the researchers infused N-acetylcysteine (NAC), an antioxidant that boosts performance in the liver, into the fetal liver, it did not reproduce the results of SOD3. This suggests the naturally produced SOD3 from exercise
during pregnancy is pivotal for the offspring's metabolic wellbeing.

Implications for the future Given the simplicity and cost-effectiveness
of exercise, encouraging mothers to exercise could help reverse the
alarming rates of obesity and type-2 diabetes.

The merits of SOD3 may not be limited to the metabolism stresses Kusuyama.

"There may be wider benefits of this protein on other organs in the
child. We are currently looking into the modifications in placenta
tissue brought about by SOD3 that may have positive lifelong impacts on children." The authors caution the study is only at the preclinical stage
and its applicability to humans requires further studies. Additionally,
certain aspects of the signaling pathway require further investigation.


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


========================================================================== Journal Reference:
1. Joji Kusuyama, Nathan S. Makarewicz, Brent G. Albertson, Ana Barbara
Alves-Wagner, Royce H. Conlin, Noah B Prince, Christiano
R. R. Alves, Krithika Ramachandran, Chisayo Kozuka, Yang Xiudong,
Yang Xia, Michael F.

Hirshman, Toshihisa Hatta, Ryoichi Nagatomi, Eva S. Nozik, Laurie J.

Goodyear. Maternal Exercise-Induced SOD3 Reverses the Deleterious
Effects of Maternal High Fat Diet on Offspring Metabolism
Through Stabilization of H3K4me3 and Protection Against WDR82
Carbonylation. Diabetes, 2022; DOI: 10.2337/db21-0706 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220414110845.htm

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