iiinova — where your digital self keeps evolving

"Bioimpedance analysis (BIA) and conventional anthropometric methods may rely on body composition prediction equations for which the development reference method may not be specified or may be mislabeled by the manufacturer." 6/7

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".. the outdated umbrella term ‘‘lean body mass’’ is frequently used to describe the results of body composition evaluations observed in studies of GLP-1RAs even though it lacks specificity." 5/7

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An abundance of publications is drawing attention to the decrements in skeletal muscle mass accompanying weight loss mediated by glucagon-like peptide-1 receptor agonists. Herein we advance three sugg...

"... these kinds of observations again show that a measured component such as FFM (fat-free mass) or LST (lean soft tissue) cannot simply be assumed to be directly proportional to skeletal muscle mass..." 4/7 www.cell.com/cell-metabol...

cell.com

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Below are a few quotes from some of the scientists, such as Steven Heymsfield, that have spent decades studying human body composition: 3/7

For a lot of people using weight loss drugs, loss of fat-free mass might not be a real problem. It is only within the last few years that researchers have started investigating this. 2/7

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Vægttabsmedicin – Op til hver tredje kilo, du taber kan være muskelmasse

One cannot automatically assume that fat-free body mass accurately reflects skeletal muscle mass, as done in this piece👇 1/7 "Weight-Loss Medication: Up to One-Third of the Weight You Lose May Be Muscle Mass" www.fitnews.dk/vaegttabsmed...

fitnews.dk

Vægttabsmedicin som Mounjaro og Wegovy giver typisk hurtige og store vægttab. Men uden en plan og løbende måling af kropssammensætningen

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With the risk that this post might backfire at some point, let’s pay more attention to Nurse’s Angel and Kaelin’s bricks. What do you think it takes to change these aspects of Academia? 14/14

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“… the goal of a paper seems to have shifted from validating specific conclusions to making the broadest possible assertions. The danger is that papers are increasingly like grand mansions of straw, rather than sturdy houses of brick.” 13/14

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Publish houses of brick, not mansions of straw - Nature

And regarding bricks, let’s end by an underappreciated quote from William G. Kaelin Jr’s 2017 World View-piece in @nature.com encouraging us to: ‘Publish houses of brick, not mansions of straw’. 12/14 www.nature.com/articles/545...

nature.com

Papers need to include fewer claims and more proof to make the scientific literature more reliable, warns William G. Kaelin Jr.

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“When I look at the story of GLP-1, it’s 40 years of careful science... It just took a series of careful iterative studies, brick by brick, to build a scientific foundation. So, I think the message of GLP-1 is not - get rich quick.”

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In cardiometabolic research the recipe for doing rigorous and impactful science is nicely captured in ‘The GLP-1 Story’ by @easdnews.bsky.social, illustrated by this quote from @danieljdrucker.bsky.social: 10/14 easd-elearning.eu/episode/367/...

easd-elearning.eu

The GLP-1 Story

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… You establish a reputation that when you publish something, it’s true. When you publish something it’s clear. The work was well thought out. The controls were powerful. And you came up with clever corroborating lines of evidence to support your conclusions.” 9/14

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William Kaelin, Nobel Prize in Physiology or Medicine: How should you measure success?

Unfortunately, the Angel - and its advice to dig deeper - are suffering in today’s science. And so is this important take on how you should measure ‘success’ - from another Nobel Laureate, William G. Kaelin Jr: 8/14 www.youtube.com/watch?v=JpvX...

youtube.com

YouTube video by Nobel Prize

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The experience of Paul Nurse illustrates that by listening to the Angel’s advice, and chasing the unexpected result, you are not only likely to get closer to the truth, you might also make a major discovery. 7/14

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I guess most scientists can relate to this dilemma. And if you have never encountered the Angel on your shoulder, or barely hear it, you should probably quit science. 6/14

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.. But the angel told him to dig deeper and try to understand why the experiments weren’t working. He then woke up in a cold sweat, but decided to follow the angel’s advice. After two days, he succeeded – and was rewarded with a slew of unexpected insights.” 5/14

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The devil told him that as he was the only one who knew the experiments hadn’t worked out as expected, he should just ignore it and publish the “right” outcome... 4/14

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"After a day spent wrestling with the problem, he had a dream in which he found himself with a devil sitting on one shoulder, and an angel on the other... 3/14 ccc.ox.ac.uk/sites/defaul...

ccc.ox.ac.uk

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In the research that led to the discovery of cell cycle control (and 1/3 of the @nobelprize.org in Physiology or Medicine 2001), Paul Nurse was at one point finding himself battling with an annoying result that did not fit his idea about what the experiment should show.. 2/14

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Listen to the Angel on your shoulder – and build your science with bricks 🧱 1/14 🧵

<fc>GLP</fc>‐1 Receptor Agonists, Gastric Emptying, and Mechanisms of Weight Loss

The effect of GLP-1RAs on insulin secretion has also been highlighted as a potential contributor of GLP-1RA-induced weight loss. See this recent Letter to the Editor of 'Obesity' from Arne Astrup and @davidludwigmd.bsky.social: onlinelibrary.wiley.com/doi/10.1002/...

onlinelibrary.wiley.com

Click on the article title to read more.

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In our article, we propose a series of experiments and considerations for testing the fuel partitioning hypothesis of GLP-1RA-induced weight loss. But you might have other ideas - how would you suggest to test this hypothesis? 11/16 @cbmr.science

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Thirdly, we are not the only ones with these speculations 👇 @sharshj.bsky.social 9/16

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Mitochondrial control of fuel switching via carnitine biosynthesis

Secondly, impairing the body’s ability to burn fat (i.e. burning of lipids that are transported into the mitochondria via the carnitine shuttle) diminishes the reduction in food intake and weight induced by semaglutide 8/16 www.science.org/doi/10.1126/...

science.org

Environmental adaptation often involves a shift in energy utilization toward mitochondrial fatty acid oxidation, which requires carnitine. Besides dietary sources of animal origin, carnitine biosynthe...

Whether this increase in fat combustion is simply a consequence of the calorie deficit caused by the drugs, or whether it also helps drive the calorie deficit is not fully clear. However, there are indications that the latter might be the case. 6/16

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Numerous studies show that GLP-1RAs, and other obesity drugs such as tirzepatide, lead the body to burn more fat - illustrated by @sharshj.bsky.social and Julio Ayala demonstrating an increase in fat oxidation in the initial phase of weight loss caused by semaglutide treatment in mice 5/16

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In a Forum article led by Mark Friedman and published in the August issue of @cp-trendsendomet.bsky.social, we propose that changes in metabolic fuel partitioning triggered by GLP-1-RAs might help explain why these drugs make us lose weight. 4/16

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But is that the entire explanation for why these drugs are so effective at shrinking fat stores - or is there an additional, and indirect, mechanism involving peripheral tissues that helps suppress appetite and lower body weight? 3/16

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Wegovy, and other long-acting GLP-1 receptor agonists (GLP-1RAs), lowers body weight by suppressing appetite. This appears to occur via direct activation of appetite-regulating brain circuits. 2/16

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Could Wegovy’s weight-lowering effect be caused by how the drug affects fuel metabolism? 1/16

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Their findings were published in @pnas.org in 2015. Let’s strive to give credit where credit is due!

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The original discovery of Lac-Phe (and other N-lactoyl-amino acids) as exercise-induced metabolites was made by Robert Jansen, Koen van de Wetering and colleagues in blood drawn from themselves after running up the stairs at The Netherlands Cancer Institute.

In contrast to what is often stated, the highly-cited 2022 Nature paper on Lac-Phe did not discover Lac-Phe as an exercise-induced metabolite. It re-discovered it (and expanded this finding to other mammalian species+showed it to be among the top exercise-induced metabolites).

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