A new discovery reveals that astrocytes, star-shaped cells in the brain, play a key role in regulating fat metabolism and obesity. These cells act on a cluster of neurons, known as the GABRA5 cluster, effectively acting as a “switch” for weight regulation.

The MAO-B enzyme in these astrocytes was identified as a target for obesity treatment, influencing GABA secretion and thus weight regulation.

KDS2010, a selective and reversible MAO-B inhibitor, successfully led to weight loss in obese mice without impacting their food intake, even while consuming a high-fat diet, and is now in Phase 1 clinical trials.

  • @wahming
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    310 months ago

    Calories in calories out is a pretty discredited theory, if that’s what you are referring to. The human body is not a closed system, so laws of physics is about as irrelevant as possible. The body can influence how much energy to absorb and burn, within limits.

    Seriously, all the points you’re bringing up were fully addressed at some point in the article. It’s fine if you can’t be bothered to read, but it makes no sense to belittle it in that case.

    • @Sodis@feddit.de
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      210 months ago

      The body can influence how much energy to absorb and burn, within limits.

      Yes and with that you have an upper limit of how much energy food can give to your body. If your body does take less than this energy, you will lose weight even faster. It can’t take more energy than is provided by the food. Raise your exercise level above your maximum intake and you will lose weight. It’s thermodynamics.

      • @wahming
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        210 months ago

        Seriously, all the points you’re bringing up were fully addressed at some point in the article. It’s fine if you can’t be bothered to read, but it makes no sense to belittle it in that case.

        • sorry, but i have to agree with @Sodis here. Calories in Calories out provides hard physical limits. If your article does nit acknowledge such fundamentals, it is questionable how reliable it is otherwise.

          • @wahming
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            210 months ago

            It does. It’s amazing how many people will debate without reading the material under discussion. What do you want me to do, paste the whole thing in a comment? It’s the length of a short book. I would love to discuss it, but not if nobody else has bothered reading it.

            • @Sodis@feddit.de
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              210 months ago

              I am trying, but it is just not well backed by data. The author goes on about diets all the time, grossly generalizing and totally ignoring, that it is also important how much you consume. They cite an example of France in the 1800s and say, that they ate more bread and butter (the link to the source not working). Okay, sure. And then they say, that they could still maintain their health easily, followed by the statement, that they exercised more, but this minor difference is not enough to explain it. Like, what are they going on about? In 1800 about two thirds of the population were working on farms, that’s not just “a bit more exercise”. And no word about food scarcity. People just couldn’t afford gluttony. Often enough they were just one bad harvest away from a famine. It’s ridiculous to assume, that they got to the same calorie intake on their bread, butter and dairy diet, that we have today with the amounts of sugar we eat and the affordability of food.

              And while they probably exercised more on average than we do, the minor difference in exercise isn’t enough to explain the enormous difference in weight.

              That statement is just plain wrong. Let’s say a minor difference in exercise is 50kcal a day. That’s about 6min running at 10km/h. This adds up to 18250kcal a year, which translates to over 2kg of body weight in ONE year. Multiply that by multiple years and it adds up quite fast. Keep that in mind for the following statement:

              Many of them were farmers or laborers, of course, but plenty of people in 1900 had cushy desk jobs, and those people weren’t obese either.

              Well, how did people get to these cushy desk jobs? By not available cars? How did they get their groceries? How did they clean their clothes? That’s all stuff, that takes a minimum of exercise nowadays. What did they do on their free time? It probably wasn’t sitting in front of the screen with minimal movement.

              That’s just the first of these “mysteries” and the whole thing is written in this style. They take an observation and then give an explanation for it, that fits their narrative. Alternative explanations are either not acknowledged or ruled out on flimsy evidence.

              Here, from the CICO part:

              Sources have a surprisingly hard time agreeing on just how much more we eat than our grandparents did, but all of them agree that it’s not much. Pew says calorie intake in the US increased from 2,025 calories per day in 1970 to about 2,481 calories per day in 2010. The USDA Economic Research Service estimates that calorie intake in the US increased from 2,016 calories per day in 1970 to about 2,390 calories per day in 2014. Neither of these are jaw-dropping increases.

              How are these not giant increases in calorie intake? This metric is per DAY. It adds up fast over years. We are speaking about 16kg worth of body weight in calories per year. Okay, they addressed this in the interlude:

              Studies show that people with obesity eat and expend more calories than lean people. From this study, for example, consider this sentence: “TDEE was 2404±95 kcal per day in lean and 3244±48 kcal per day in Class III obese individuals.” From this perspective, the average daily consumption per Pew being 2,481 calories per day doesn’t seem like much — that’s about what lean people expend daily.

              TDEE includes exercise. Class 3 obese is a BMI of 40, so for a 1.8m tall male, that is 130kg, lean is probably at the lower end of normal, so 65kg. Then you can calculate the basal metabolic rate for both cases, leading to 1655kcal/day for the lean and 2300kcal/day for the obese. The difference is exercise. So lean people burn ~800kcal worth of exercise while obese people burn ~900kcal, but at double the weight. Since calorie burning during exercise goes linear with weight, you can conclude, that lean people workout more than obese people. So their argument does not work.

              I never said, that it would be easy to lose weight. It definitely is hard. Your body is adapted to your lifestyle and breaking out of your habits and completely changing your lifestyle can be extremely hard. However, blaming some mysterious contaminant will not help people lose weight. Especially, when things like liquid calories tend to add a lot to your calorie intake, but your body does not really register them. Our body has evolved to control its body weight over thousands of years to a different type of diet. I do really not know, why the authors think, that subjecting it to the modern day achievements of high calorie foods and liquid calories will not affect this balance.

              • @wahming
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                210 months ago

                Thanks! This is exactly what I was hoping for, some critical analysis of the article’s methodology and conclusions. I’m not debating any of your claims above, just gonna use them as a jumping off point for more reading.

    • @LogarithmicCamel@feddit.uk
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      210 months ago

      This is not true. The laws of thermodynamics apply to open systems as well as long as you take into account the energy that enters and leaves the system, which is exactly what calories in, calories out mean. The brain influencing how many calories are spent is just part of calories out. What doesn’t work is equating calories out with imprecise estimates from websites, watches etc, or equating calories in with imprecise calorie counts from food labels that people often miscount anyway. But when calories are carefully measured by scientists (i.e. in a metabolic chamber) and everything is accounted for, it’s calories in, calories out all the way.