Obesity Breakthrough: Biologists Discover How To Counteract Effects of High-Fat Diet

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University of California, Irvine biologists have discovered that by eliminating the SAPS3 component of the AMPK protein complex, mice were able to maintain a normal energy balance even when consuming a high-fat diet. This finding, published in Nature Communications, reveals the potential for developing molecules that inhibit SAPS3 to help restore metabolic balance and combat metabolic disorders like obesity, diabetes, and fatty liver disease. As metabolic-related diseases continue to rise globally, this research could lead to a new approach in treating these conditions.

Biologists discover removing a protein inhibitor restores metabolic balance.

UC Irvine biologists found that removing the SAPS3 component in mice allowed them to maintain a normal energy balance despite consuming a high-fat diet. This discovery could lead to treatments for obesity, diabetes, and other metabolic disorders by targeting SAPS3 inhibition.

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 (UCI) biologists have made a key finding about how to ward off harmful effects caused by a high-fat diet. Their study was published recently in the scientific journal 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.

Mei Kong

Mei Kong is a professor of molecular biology & biochemistry and the study’s corresponding author. Credit: UCI School of Biological Sciences

“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.

Reference: “SAPS3 subunit of protein phosphatase 6 is an AMPK inhibitor and controls metabolic homeostasis upon dietary challenge in male mice” by Ying Yang, Michael A. Reid, Eric A. Hanse, Haiqing Li, Yuanding Li, Bryan I. Ruiz, Qi Fan and Mei Kong, 13 March 2023, Nature Communications.
DOI: 10.1038/s41467-023-36809-1

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

9 Comments on "Obesity Breakthrough: Biologists Discover How To Counteract Effects of High-Fat Diet"

  1. More DRUGS!!!! Moar!!!!!!!!!!
    Or just eat healthy and dont stuff your face constantly with over processed carbs and sugars??
    Nah that wouldnt make big pharma and the health industry trillions!

    • Torbjörn Larsson | April 10, 2023 at 1:30 am | Reply

      This is just a drug candidate at this stage.

      But if it proves useful and harmless enough it could make people trillions of dollars in avoided health costs. What would be the harm in that?

      Meanwhile, conspiracy theories like the one proposed here – “big pharma” – is harmful since it unnecessarily detracts from medicine and science and their benefits.

  2. Charles G. Shaver | April 7, 2023 at 7:13 am | Reply

    Not sure it applies to lab mice but long-term chronic nearly subclinical non-IgE-mediated allergy reactions, not calories, carbs, fats or oils can cause fatigue, sluggish metabolism, more sedentary lifestyle and weight gain in humans, especially if aggravated with added ‘cultured-free’ MSG, which can cross the blood brain barrier, and modified common allergen soy protein. Surely, deliberately feeding the mice a high fat diet reduced their intakes of proteins?

    • Torbjörn Larsson | April 10, 2023 at 1:39 am | Reply

      Mono Sodium Glutamate – MSG – is a necessary amino acid, not harmful as such but its absence is, and a component of food.

      “Previously, there was no value for acceptable daily intake, ADI, but in the last evaluation in 2017, the European Food Safety Authority, Efsa, set an ADI value of 30 mg/kg body weight per day. Acceptable daily intake is the amount one can eat daily throughout life without risk to health.

      Based on the new ADI value, Efsa concludes that many people get too much glutamate when taking into account the total intake of both natural glutamic acid from the diet and glutamate as a food additive. Even if the ADI is set with a large margin of safety, this is not desirable. Efsa therefore recommends that the EU Commission review the use of these food additives.

      Following EFSA’s evaluation, the European Commission has started discussions on limiting the use of glutamate as a food additive. Then it is about which foods and in what amounts the additives must be approved.”

      [Swedish Food Agency]

      There is no restriction on MGA as of yet and it has no direct correlation with obesity. The reason why EU is looking into this is that in clinical studies, when it is given directly into the blood stream, this is one os smaller group of amino acids that has shown effects on the central nervous system.

      Maybe we should stick to the topic instead of making unsubstantiated tangential claims (no references, not the main topic)?

      • Charles G. Shaver | April 10, 2023 at 8:48 am | Reply

        Thanks for the feedback, Torbjörn, but, perhaps, I should have included a phrase I often do in my comments: “as opposed to natural ‘protein bound'” (e.g., cheese, tomatoes, seaweed) MSG, which as I understand it cannot cross the blood brain barrier in that form. And, while “glutamate” is an essential amino acid, ‘cultured free’ MSG added as an alleged “flavor enhancer” is not. Because my (Dr. Arthur F. Coca’s, by 1935) kind of allergies are not yet recognized, studied and/or practiced by mainstream medicine, I can only suggest (based on personal experience and statistics) that ‘added’ MSG aggravates practically harmless individual allergy reactions to become chronic and deadly dangerous, long term (highly individual, many individual variables). None of the ‘added’ MSG studies I’ve read of ever included the allergy factor. Statistically, in the US, the FDA approved the expanded use of added MSG in 1980 and the obesity/diabetes epidemic presented by 1990 (CDC/NCHS data); check it out.

  3. I’m vegan for the animals. I eat complex carbs. I can control myself with discipline. I should weigh a ton, but my weight is stable (below 110) pounds. It’s the meat, dairy, eggs and sea-life that add fat, cholesterol and residues of pesticides and hormones to the diet of carnivores. So, go ahead and enjoy your fad diets, folks!

  4. Follow a low carb diet and fat just passes right through you. No need for a pill. I ate over 3 dozen eggs a week, blocks of cheese and loads of bacon before on a low carb diet and still lost 50 pounds in 3 months and my cholesterol was the best my doctor ever saw (3 points from being off the bottom of the risk chart using combined LDL/HDL/Triglycerides). I now make a variety of wraps using OLE KETO wraps with lots of spinach, peppers and onions plus meat and cheese including burrito sized “pizza rolls” that are low carb and taste awesome. Want dessert? Try blueberries or raspberries with zero calorie whipped cream and a little liquid sucralose on the berries. It’s like berry pie without the disgusting pointless crust. Plus 2.5 POUNDS of frozen blueberries are only 490 calories and at least here cost only $7.99 so a bowl of them is less calories than eating a low-fat yogurt. Plus they have a chemical naturally in them that keeps blood sugar from spiking (and raspberries are naturally low carb).

  5. Torbjörn Larsson | April 10, 2023 at 1:42 am | Reply

    Vegan is a fad diet, and it is not proven to be harmless.

    That said, most people can eat more non-meat stuff, which improves health, climate and animal welfare.

    • Torbjörn Larsson | April 10, 2023 at 1:47 am | Reply

      The comment was supposed to be a response to Carol. But I can repeat the response to Frodo’s similar fad diet.

      Eat healthy, that benefits you, the economy and the climate (since the cheapest food stuff is likely most effectively produced). Such a food basis should be informed on at your nation’s food agencies web sites [or else see the Swedish Food Agency site], and it does not include fad diets.

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