Adipose tissue deficiency of hormone-sensitive lipase causes fatty liver in mice
Bibliographic record
Abstract
Fatty liver is a major health problem worldwide.People with hereditary deficiency of hormone-sensitive lipase (HSL) are reported to develop fatty liver.In this study, systemic and tissue-specific HSL-deficient mice were used as models to explore the underlying mechanism of this association.We found that systemic HSL deficient mice developed fatty liver in an age-dependent fashion between 3 and 8 months of age.To further explore the mechanism of fatty liver in HSL deficiency, liver-specific HSL knockout mice were created.Surprisingly, liver HSL deficiency did not influence liver fat content, suggesting that fatty liver in HSL deficiency is not liver autonomous.Given the importance of adipose tissue in systemic triglyceride metabolism, we created adipose-specific HSL knockout mice and found that adipose HSL deficiency, to a similar extent as systemic HSL deficiency, causes age-dependent fatty liver in mice.Mechanistic study revealed that deficiency of HSL in adipose tissue caused inflammatory macrophage infiltrates, progressive lipodystrophy, abnormal adipokine secretion and systemic insulin resistance.These changes in adipose tissue were associated with a constellation of changes in liver: low levels of fatty acid oxidation, of very low density lipoprotein secretion and of triglyceride hydrolase activity, each favoring the development of hepatic steatosis.In conclusion, HSL-deficient mice revealed a complex interorgan interaction between adipose tissue and liver: the role of HSL in the liver is minimal but adipose tissue deficiency of HSL can cause age-dependent hepatic steatosis.Adipose tissue is a potential target for treating the hepatic steatosis of HSL deficiency. Author summaryFatty liver is a major complication of obesity and of type 2 diabetes mellitus.It carries a high risk of cirrhosis and liver cancer.In fatty liver, triglycerides accumulate to high levels in the cytoplasm of hepatocytes.Triglycerides are degraded by lipolysis, which has been most studied in fat cells where its three steps are catalyzed by different enzymes.The second step, hydrolysis of diglyceride to a monoglyceride, can be mediated by hormone-sensitive lipase (HSL).Patients with genetic deficiency of HSL have fatty liver.In this study, we found that systemic HSL deficient mice developed fatty liver with aging.To study the
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.003 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.003 |
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 source (direct Gemma or distilled Codex), 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".