Duodenal-jejunal bypass maintains hepatic S-adenosylmethionine/S-homocysteine ratio in diet-induced obese rats

Kim, Mi-Kyung; Rho, Yunmee; Park, Rhoeun; Jung, Jeeyoun; Hwang, Gwi Seo; Seo, Youn Kyoung; Seo, Ji Hae; Heo, Yoonseok; Ha, Tae Kyung; Ha, Eunyoung

doi:10.1016/j.soard.2021.02.011

Cited by 4 publications

(3 citation statements)

References 28 publications

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“…The previous cell biology data also show that like SAM, the binding of SAH to hSAMTOR can disrupt the interaction of hSAMTOR with GATOR1-KICSTOR and inhibit the GATOR1 GAP activity in mTORC1 signaling (22). As the concentrations of SAM and SAH in cells are estimated to be at similar levels (38)(39)(40)(41), these results suggest that SAH might be able to regulate the function of SAMTOR in mTORC1 signaling in the same manner as SAM.…”

Section: Discussionmentioning

confidence: 61%

Molecular mechanism of S -adenosylmethionine sensing by SAMTOR in mTORC1 signaling

et al. 2022

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The mechanistic target of rapamycin–mLST8-raptor complex (mTORC1) functions as a central regulator of cell growth and metabolism in response to changes in nutrient signals such as amino acids. SAMTOR is an S -adenosylmethionine (SAM) sensor, which regulates the mTORC1 activity through its interaction with the GTPase-activating protein activity toward Rags-1 (GATOR1)-KPTN, ITFG2, C12orf66 and SZT2-containing regulator (KICSTOR) complex. In this work, we report the crystal structures of Drosophila melanogaster SAMTOR in apo form and in complex with SAM. SAMTOR comprises an N-terminal helical domain and a C-terminal SAM-dependent methyltransferase (MTase) domain. The MTase domain contains the SAM-binding site and the potential GATOR1-KICSTOR–binding site. The helical domain functions as a molecular switch, which undergoes conformational change upon SAM binding and thereby modulates the interaction of SAMTOR with GATOR1-KICSTOR. The functional roles of the key residues and the helical domain are validated by functional assays. Our structural and functional data together reveal the molecular mechanism of the SAM sensing of SAMTOR and its functional role in mTORC1 signaling.

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Section: Discussionmentioning

confidence: 61%

Molecular mechanism of S -adenosylmethionine sensing by SAMTOR in mTORC1 signaling

et al. 2022

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“…Our results are in agreement with a recent systematic review on the metabolic changes associated with bariatric surgery in general and a recent study examining the effects of gastric bypass on the metabolic composition of the portal blood, both of which identified glycine, serine, and threonine metabolism and cysteine and methionine metabolism as the metabolic pathways uniquely affected by bariatric surgery 48,49 . A decrease in SAM-synthesizing enzymes was described in mice following duodenal-jejunal bypass (DJB) 50 . A similar profile of increased levels of methyl donors and acceptors as seen in our study was observed in humans following Roux-en-Y gastric bypass, where levels of both methionine and PE were found to inversely correlated with insulin resistance following surgery 51 .…”

Section: Discussionmentioning

confidence: 99%

A multiomics comparison of weight loss interventions shows the distinct effects of bariatric surgery and intermittent fasting on hepatic metabolism

Haran

Bergel

Kleiman

et al. 2022

Preprint

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The prevalence of obesity and non-alcoholic fatty liver (NAFL) is steadily increasing. Weight loss can lead to improvement in NAFL in patients and in model organisms. Weight loss can be achieved through either dietary and lifestyle interventions, pharmacotherapy, and bariatric surgery. Some interventions, such as intermittent fasting, have been purported to have benefits beyond those conferred by weight loss alone. In this study, rats were provided a high-fat, high-sucrose diet for 7 weeks and then were assigned to strict caloric restriction with intermittent fasting (IF-CR) or to sleeve gastrectomy (SG) bariatric surgery, achieving equivalent weight loss. The two interventions were compared to ad-libitum fed controls. The metabolome of the blood entering the liver was analyzed in the three experimental groups, as well as the metabolome and transcriptome of the liver under fasting conditions, to test how different means of weight loss affect the input of the liver and hepatic metabolism. Surprisingly, the two interventions had different and often opposite effects on the composition of portal blood and liver metabolites. IF-CR resulted in sweeping changes across multiple central metabolic pathways, including an increase in de novo lipogenesis and triglyceride export, and upregulation of glycolysis, citric acid cycle, and the pentose phosphate pathway, as well as an increase in glycogen storage. Meanwhile, the effects of SG concentrated on one-carbon metabolic pathways, with changes in metabolite and transcript levels pointing to decreased transmethylation and methionine cycle activity, with downstream effects on levels of glutathione and the hepatic oxidative state. In conclusion, our study highlights how different means of weight loss affect distinct metabolic pathways and demonstrates a unique effect of bariatric surgery on hepatic one-carbon and redox pathways.

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“…Some effect of bariatric surgery on hepatic one-carbon metabolism, although not well characterized, has been identified in several human and animal studies. 22 , 23 , 24 , 25 …”

Section: Introductionmentioning

confidence: 99%

Differential effects of bariatric surgery and caloric restriction on hepatic one-carbon and fatty acid metabolism

et al. 2023

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Duodenal-jejunal bypass maintains hepatic S-adenosylmethionine/S-homocysteine ratio in diet-induced obese rats

Cited by 4 publications

References 28 publications

Molecular mechanism of S -adenosylmethionine sensing by SAMTOR in mTORC1 signaling

Molecular mechanism of S -adenosylmethionine sensing by SAMTOR in mTORC1 signaling

A multiomics comparison of weight loss interventions shows the distinct effects of bariatric surgery and intermittent fasting on hepatic metabolism

Differential effects of bariatric surgery and caloric restriction on hepatic one-carbon and fatty acid metabolism

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