Tissue Distribution of S‐(2‐Succino)cysteine (2SC), a Biomarker of Mitochondrial Stress in Obesity and Diabetes
Bibliographic record
Abstract
S-(2-succino)cysteine (2SC) is a chemical modification of proteins produced by reaction of fumarate with thiol groups in protein, a process known as succination. We propose to use the name S-(2-succino)cysteine (instead of S-(2-succinyl)cysteine) from this point on. This is to distinguish protein succination (in which fumarate forms a thioether linkage with cysteine residues) from succinylation (in which an ester, thioester or amide bond would be formed). Succination of proteins is increased in muscle of type 1 diabetic rats and in adipose tissue in type 2 diabetic mice. The increase in 2SC is a direct result of tissue accumulation of fumarate in response to nutrient excess and resultant mitochondrial stress in diabetes. In this study, we examine the breadth of succination of tissue proteins in the db/db type 2 model of diabetes. We also determined the extent of succination in epididymal adipocytes of type 1 (Akita, streptozotocin (STZ)) and type 2 (ob/ob, db/db) diabetic mice, in diet-induced obese (DIO) mice, and in the adipose tissue of ground squirrels in various stages of hibernation. While succination was not increased in most tissues (brain, heart, kidney, liver, skeletal muscle) in the db/db model of diabetes, it was increased in all adipose beds of type 2 diabetic and DIO mice in comparison to their controls. Succination was not increased in adipocytes of type 1 diabetic mice. Adipose tissue from hibernating (HIB) 13-lined ground squirrels was also studied to determine if obesity in the absence of hyperglycemia affected succination of proteins. There were no differences in succination of proteins in brown or white adipose tissue over the torpor-arousal cycle. We conclude that 2SC is a biomarker of nutrient excess and mitochondrial stress in adipose tissue, increasing under the hyperglycemic and insulin resistant conditions associated with type 2 diabetes and obesity.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".