Great! Just what we needed, a medication for guilt...

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Or placebo, why are we trying to cure guilt?

Abstract: >This study aims to investigate how metformin (Met) affects muscle tissue by evaluating the drug effects on proliferating, differentiating, and differentiated C2C12 cells. Moreover, we also investigated the role of 5’-adenosine monophosphate-activated protein kinase (AMPK) in the mechanism of action of Met. C2C12 myoblasts were cultured in growth medium with or without Met (250μM, 1mM and 10mM) for different times. Cell proliferation was evaluated by MTT assay, while cell toxicity was assessed by Trypan Blue exclusion test and Lactate Dehydrogenase release. Fluorescence Activated Cell Sorting analysis was performed to study cell cycle. Differentiating myoblasts were incubated in differentiation medium (DM) with or without 10mM Met. For experiments on myotubes, C2C12 were induced to differentiate in DM, and then treated with Met at scalar concentrations and for different times. Western blotting was performed to evaluate the expression of proteins involved in myoblast differentiation, muscle function and metabolism. In differentiating C2C12, Met inhibited cell differentiation, arrested cell cycle progression in G2/M phase and reduced the expression of cyclin-dependent kinase inhibitor 1. These effects were accompanied by activation of AMPK and modulation of the myogenic regulatory factors. Comparable results were obtained in myotubes. The use of Compound C, a specific inhibitor of AMPK, counteracted the above-mentioned Met effects. We reported that Met inhibits C2C12 differentiation probably by blocking cell-cycle progression and preventing cells permanent exit from cell-cycle. Moreover, our study provides solid evidence that most of the effects of Met on myoblasts and myotubes are mediated by AMPK.

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Abstract:

Background

In addition to its contractile properties and role in movement, skeletal muscle plays an important function in regulating whole-body glucose and lipid metabolism. A central component of such regulation is mitochondria, whose quality and function are essential in maintaining proper metabolic homeostasis, with defects in processes such as autophagy and mitophagy involved in mitochondria quality control impairing skeletal muscle mass and function, and potentially leading to a number of associated diseases. Cold exposure has been reported to markedly induce metabolic remodeling and enhance insulin sensitivity in the whole body by regulating mitochondrial biogenesis. However, changes in lipid metabolism and lipidomic profiles in skeletal muscle in response to cold exposure are unclear. Here, we generated lipidomic or transcriptome profiles of mouse skeletal muscle following cold induction, to dissect the molecular mechanisms regulating lipid metabolism upon acute cold treatment.

Results

Our results indicated that short-term cold exposure (3 days) can lead to a significant increase in intramuscular fat deposition. Lipidomic analyses revealed that a cold challenge altered the overall lipid composition by increasing the content of triglyceride (TG), lysophosphatidylcholine (LPC), and lysophosphatidylethanolamine (LPE), while decreasing sphingomyelin (SM), validating lipid remodeling during the cold environment. In addition, RNA-seq and qPCR analysis showed that cold exposure promoted the expression of genes related to lipolysis and fatty acid biosynthesis. These marked changes in metabolic effects were associated with mitophagy and muscle signaling pathways, which were accompanied by increased TG deposition and impaired fatty acid oxidation. Mechanistically, HIF-1α signaling was highly activated in response to the cold challenge, which may contribute to intramuscular fat deposition and enhanced mitophagy in a cold environment.

Conclusions

Overall, our data revealed the adaptive changes of skeletal muscle associated with lipidomic and transcriptomic profiles upon cold exposure. We described the significant alterations in the composition of specific lipid species and expression of genes involved in glucose and fatty acid metabolism. Cold-mediated mitophagy may play a critical role in modulating lipid metabolism in skeletal muscle, which is precisely regulated by HIF-1α signaling.

Welcome to r/science! This is a heavily moderated subreddit in order to keep the discussion on science. However, we recognize that many people want to discuss how they feel the research relates to their own personal lives, so to give people a space to do that, personal anecdotes are allowed as responses to this comment. Any anecdotal comments elsewhere in the discussion will be removed and our normal comment rules apply to all other comments.

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Kind of like say if you wash your hands repeatedly.

Study re-confirms that communication is important in relationships.

Lying to ourselves helps us.

How very, human

No, they're not carnivores - they're omnivores. They'll quite happily eat vegetables - carrot, celery, potatoes, beets, and fruit - berries, and even citrus.

Wolves are also omnivorous.

Maybe she'll call after being alone for a long time. Or maybe not and she'll just piss all her money away instead of reaching any of her goals.

She's always been terrible with money and was way worse before we met.

Well yeah, she specifically said to be the stay at home person.

Would have been nice to have had some communication that it was no longer enough.

As long as it’s good for you, absolutely. But there are others who would become resentful that they are prevented from leading the life they want to live.

Absolutely. I have a high libido (I’m a woman) & my abusive ex-husband used it to manipulate & torment me. No one of any gender should be punished for having a high libido.

We just call them jelly beans. No need to get fancy.

I mean it’s not always a deal breaker. I’ve always wanted to travel but would give that up for the right person and did.

I think back on it sometimes but I don’t blame them. I made the decision and they aren’t adverse to taking vacations so that’s a good middle ground for me.

I wish I really understood this 10 years ago..

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That’s a fair point. But it should hopefully give you a better idea if your goals are compatible. With that said, obviously people change & there are no guarantees- especially in marriage.

Why is cannabis still illegal federally? People are suffering.

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My goal for me at the end of the week is to rest up from being exhausted.

Her goal for me at the end of the week is to do anything but rest.

Yeah same. I do not want something so expensive it would hurt if it got lost or broke in my finger. Let’s improve our lives together so we can spend more free time together instead.

The people that are more naturally equipped to fill the support roles like this never get the recognition they deserve because a lot of it is intangible (less stress on the other person) or isn’t noticed (like good technology, good support is almost never noticed when it works. When the house is clean and groceries are bought within the budget and making every purchase count and making the best possible use of money by hours of research)

I’m that person too and it took my husband living on his own to realize how much I take care of for him. He forgets time to time still so I will get busy doing something more tangibly productive and stop doing the other stuff but it never lasts long.

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Most people already do the kids thing then the woman changes because the man can't leave without it costing him a fortune.