Sakamoto Lab

A photo of a Nobel medal

BREAKING: The Nobel Prize in Physiology or Medicine has been awarded jointly to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi "for their discoveries concerning peripheral immune tolerance"

Stay tuned for more.
#NobelPrize

Common and distinct roles of AMPKγ isoforms in small-molecule activator-stimulated glucose uptake in mouse skeletal muscle Objective: Small-molecule activators targeting the allosteric drug and metabolite (ADaM) site of AMPK enhance insulin-independent glucose uptake in skeletal muscle and lower glucose in preclinical mod...

Check out our latest preprint from the lab, spearheaded by researcher @itsmedipsikha.bsky.social , investigating the distinctive roles of regulatory gamma subunits of the AMPK protein complex in small molecule activator-stimulated skeletal muscle glucose uptake.
www.biorxiv.org/content/10.1...

From NAFLD to MASLD: implications of the new nomenclature for preclinical and clinical research - Nature Metabolism Non-alcoholic liver disease (NAFLD) is now metabolic dysfunction-associated steatotic liver disease (MASLD), emphasizing the key metabolic factors of obesity, insulin resistance, vascular dysfunction and dyslipidaemia. Here, we discuss impacts on the existing body of clinical and preclinical liver disease research and on research moving forward.

#Throwback 🧪

COMMENT | From NAFLD to MASLD: implications of the new nomenclature for preclinical and clinical research

C Hsu & R Loomba

Congratulations to the lead authors, to other members of the @labsakamoto.bsky.social and all other co-authors! @keisakamoto.bsky.social @zeqiraj.bsky.social @cbmr.science

The structure of BAY-3827 with wild-type AMPK α2 kinase domain by @zeqiraj.bsky.social & postdoc Mohd. Syed Ayengar helped determine the mechanism of action of this compound and the limitations for its use, addressing a long-standing challenge in the field: the absence of specific AMPK inhibitors.

BAY-3827 inhibited ~30% of AMPK-dependent genes in mouse primary hepatocytes and reversed AMPK-inhibited lipogenesis. 2/3

Mechanism and cellular actions of the potent AMPK inhibitor BAY-3827 The mechanism and unique molecular/cellular features of the potent and selective AMPK inhibitor BAY-3827 are unraveled.

Latest publication from the lab spearheaded by @shoreseashell.bsky.social & in collaboration with @zeqiraj.bsky.social is out. Using structural, biochemical & computational tools, this work sheds light on the mechanism of action of BAY-3827 in inhibiting #AMPK 1/3
www.science.org/doi/full/10....

Last week @labsakamoto.bsky.social members participated in the #DHL Relay Copenhagen with one running team and one walking team! This was the lab's 5th year participating in this event and each year we get better with our performance😀
& this year was @keisakamoto.bsky.social personal best 🙌🍾

RNA droplets that grow and segregate by ribozyme catalysis. Check out our latest preprint www.biorxiv.org/content/10.1101/2025.08.29.673008v1

Congratulations to Researcher @itsmedipsikha.bsky.social for being one of the recipients of the EFSD/Lilly Young Investigator Awards! We celebrated her achievement with some cakes and bubbles earlier 🥳 @easdnews.bsky.social @cbmr.science

www.europeandiabetesfoundation.org/recipients/e...

A missing enzyme-rescue metabolite as cause of a rare skeletal dysplasia - Nature In mammals, the enzyme TGDS produces UDP-4-keto-6-deoxyglucose, which binds to the catalytic pocket of UDP-xylose synthase, thereby regenerating the essential NAD+ cofactor of UDP-xylose synthase...

A missing enzyme-rescue metabolite as cause of a rare skeletal dysplasia

share.google/dUNL7g7DkUle...

New PTM (lactylation) linked with #TFEB stability and increased autophagy and lysosomal activity @jcb.org

mTORC1 senses glutamine and other amino acids through GCN2 | The EMBO Journal imageimageDuring starvation, individual amino acid levels are thought to be relayed via distinct metabolic sensors, but how mTORC1 senses glutamine remains unclear. This study finds that GCN2 kinase a...

The protein kinase, GCN2 identified as the key amino acid sensor for mTORC1. @embopress.org @embojournal.org

Commentary by Researcher @itsmedipsikha.bsky.social on the emerging role of glycogen metabolism in regulating energy homeostasis in adipose tissue is out now on @natrevendo.nature.com @cbmr.science

www.nature.com/articles/s41...

Unraveling Skeletal Muscle Insulin Resistance: Molecular Mechanisms and the Restorative Role of Exercise | Circulation Research Skeletal muscle is essential for movement and maintaining energy homeostasis and is the primary tissue for insulin-stimulated glucose uptake. Skeletal muscle is composed of various cell types that hel...

Unraveling Skeletal Muscle Insulin Resistance: Molecular Mechanisms and the Restorative Role of Exercise
www.ahajournals.org/doi/10.1161/...

Targeting cardiometabolic risk in type 1 diabetes through incretin physiology People living with type 1 diabetes have significantly increased cardiovascular risk compared with the general population. Traditional risk factors include hypertension, dyslipidaemia, and obesity. How...

Among the ways for next generation GLP-1 medicines to differentiate: Efficacy, safety and outcome trials in type 1 #Diabetes www.cell.com/trends/endoc...

Sustained Weight Loss With Combined LEAP2 and Semaglutide Treatment in Mice The recent identification of liver-expressed antimicrobial peptide 2 (LEAP2) as an endogenous antagonist and inverse agonist of the growth hormone secretag

Studies in mice reveal that LEAP2 analogs have the potential to enhance the efficacy of glucagon-like peptide 1 receptor agonism and support durable #weightloss diabetesjournals.org/diabetes/art...

Altered Relaxation and Mitochondria‐Endoplasmic Reticulum Contacts Precede Major (Mal)Adaptations in Aging Skeletal Muscle and Are Prevented by Exercise Slowed relaxation and altered MERCs embody early stages of aging in muscle, and are prevented by regular exercise.

Altered Relaxation and Mitochondria-Endoplasmic Reticulum Contacts Precede Major (Mal)Adaptations in Aging Skeletal Muscle and Are Prevented by Exercise
onlinelibrary.wiley.com/doi/10.1111/...

Protagonist Enters Obesity Fray With Triple-G Pill, Eyeing 2026 Clinical Start With PN-477, Protagonist is directly going up against Eli Lilly, which is advancing retatrutide, also a triple-G agonist, in a Phase II trial.

Innovation in the #weightloss space continues with an emerging Triple G oral peptide #obesity to enter into clinical development for obesity in 2026. www.biospace.com/drug-develop...

Last week we said goodbye to Florentina, who started as a postdoc with us in early 2020. We are truly privileged for her tenacity, hardwork & diligence that helped shape our group @cbmr.science & thank her for
guiding our junior colleagues. We wish her the best for her bright future!
.

Happy to have contributed to this very interesting work ked/driven by Raid Nisr, Alison McNeilly and Graham Rena (University of Dundee). doi.org/10.1111/apha...

🔎 𝐃𝐞𝐜𝐢𝐩𝐡𝐞𝐫𝐢𝐧𝐠 𝐭𝐡𝐞 𝐆𝐈𝐏 𝐩𝐚𝐫𝐚𝐝𝐨𝐱

Why does activating the GIP receptor contribute to weight-loss, given the evidence that blocking the receptor ought to be more effective?

Prof. Jens Juul Holst outlines the evidence in Diabetes 👇

diabetesjournals.org/diabetes/art...

#GIP #GLP1 #biotech #obesity

The Use of Salt-Inducible Kinases (SIKs) Inhibitors as an Emerging Treatment for Inflammatory, Allergic, Autoimmune, Cancer, and Metabolic Diseases - PubMed The invention in this patent application relates to pyrazolo-[1,5-<i>a</i>]-pyridine derivatives represented herein as formula I and formula II. These compounds are highly active SIK inhibitors and ma...

Great reads if you're interested in learning more about Salt-Inducible Kinases #SIKs in metabolism.

pubmed.ncbi.nlm.nih.gov/40529046/
The Use of SIK Inhibitors as an Emerging Treatment...

pubmed.ncbi.nlm.nih.gov/40384110/
Salt-inducible Kinase Regulation of Adipose Tissue Metabolism

miR-30a is a critical regulator of adipose tissue fibrosis that predicts metabolically healthy #obesity in people and mice @jclinical-invest.bsky.social www.jci.org/articles/vie...

Sticky membranes of dead red blood cells obstruct small vessels Damage to the vascular lining leads to interactions with red blood cells that hint at how to treat dangerous complications of heart attack, stroke and COVID-19.

Damage to the vascular lining leads to interactions with red blood cells that hint at how to treat dangerous complications of heart attack, stroke and COVID-19

https://go.nature.com/4jyBzpe

Congratulations to all @labsakamoto.bsky.social group members for being the worthy winners of the K.I.S.S campaign! 🏆 👏 💪 Special mention to our lab manager, Marianne, for her persistence to make sure everyone gets their risk assessments done. Thanks @cbmr.science for this important initiative.

Unravelling cysteine-deficiency-associated rapid weight loss - Nature Conditional cysteine restriction in mice causes substantial weight loss, exceeding that seen with essential amino acid restriction, by activating the integrated stress and oxidative stress responses, and by unexpectedly depleting coenzyme A, leading to metabolic inefficiency.

Nature research paper: Unravelling cysteine-deficiency-associated rapid weight loss

https://go.nature.com/4mpetns

Skeletal muscle mitochondrial health in type 1 diabetes: the role of exercise capacity and lifestyle factors - Diabetologia Aims/hypothesis Previous studies reporting lower skeletal muscle mitochondrial function in type 1 diabetes did not account for cardiorespiratory fitness, a key confounder when assessing mitochondrial ...

Habitual exercise, optimal glucose management and a healthy BMI maintain mitochondrial health in individuals with type 1 #diabetes
@diabetologiajnl.bsky.social link.springer.com/article/10.1...