Job 72 - Assort Design

Request JD-000072 Medical Affairs

Audience: Medical Affairs • completed

Routing confidence: 90% • Candidates: Medical Affairs, R&D, Commercial

Routing reasons: ML fallback: low confidence (56% < 57%); The document discusses non-alcoholic steatohepatitis (NASH) and its worsening in obese patients, focusing on medical research findings.; It includes detailed scientific data on biochemical pathways, lipidomics, and translational research linking obesity to liver disease progression.; Authored and reviewed by medical professionals and scientists from a medical university, it is targeted toward healthcare and medical research professionals involved in disease understanding and treatment development.; The content is oriented toward understanding disease mechanisms which supports medical affairs functions like scientific communication and education around medical evidence.

Why Routed Here

Medical Affairs at 54.1% ▼

ML predicted Medical Affairs at 54.1% confidence. Runner-up: R And D at 29.7%.

Top contributing terms (Medical Affairs)

Term	TF-IDF	Weight	Contribution
`transplant`	0.0733	0.0783	0.0057
`obese`	0.1065	0.0438	0.0047
`why`	0.0534	0.0795	0.0042
`saturated`	0.0841	0.0483	0.0041
`health`	0.0457	0.0878	0.004
`news`	0.0454	0.0804	0.0036
`unsaturated`	0.0769	0.0461	0.0035
`lipid`	0.0489	0.0608	0.003

Runner-up: R And D (29.7%)

Term	TF-IDF	Weight	Contribution
`laboratory`	0.067	0.1008	0.0068
`mice`	0.0517	0.1035	0.0054
`alcoholic`	0.0608	0.07	0.0043
`alcoholic steatohepatitis`	0.0605	0.0524	0.0032
`and`	0.0393	0.0805	0.0032
`behind`	0.0259	0.1253	0.0032
`the laboratory`	0.0506	0.0578	0.0029
`results`	0.0238	0.0991	0.0024

All probabilities: Commercial: 16.1% · Medical Affairs: 54.1% · R And D: 29.7%

Source url

https://www.news-medical.net/news/20160120/Scientists-reveal-why-non-alcoholic-steatohepatitis-worsens-in-obese-people.aspx

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Scientists reveal why non-alcoholic steatohepatitis worsens in obese people Skip to content Menu Medical Home Life Sciences Home Become a Member Search Medical Home Life Sciences Home About Functional Food News Health A-Z Drugs Medical Devices Interviews White Papers More... 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The results may help prevent cirrhosis and liver cancer, according to co-senior authors Kenneth D. Chavin, M.D., PhD, a transplant surgeon in the MUSC Health Department of Surgery, and Lauren Ashley Cowart, PhD, Associate Professor of Biochemistry and Co-Director of the MUSC Center of Biomedical Research Excellence in Lipidomics and Pathobiology. NASH (also called non-alcoholic fatty liver disease ) has become a major cause of liver disease requiring transplant. "In my 17 years of doing liver transplants, it's gone from 4% of patients to around 20% of patients who get transplants because of NASH," says Chavin. "In 10-15 years, because of advances with Hepatitis C, it will probably become the number one reason why patients get transplants." When excess dietary fats are consumed over time, fat deposits form in the liver and NASH can develop. Early-stage NASH is typically not associated with any physical symptoms; nearly 30% of people in the U.S. have it. Though obesity is correlated with the development of NASH, the team wanted to know exactly why NASH worsens to a stage requiring transplant in certain obese people. "Obesity doesn't cause disease in every obese person and we don't understand why it does in some but not others," explains Cowart. The team suspected that inflammation stemming from a lipid molecule called sphingosine-1-phosphate (S1P) might be responsible. They'd previously discovered in other organs that S1P is increased by excess dietary saturated fat. Related Stories Nearly half of adults now live with heart disease as obesity and diabetes surge Genetic study establishes causal link between obesity and cognitive decline Study identifies genes, smoking, and obesity as pneumonia risk factors Chavin took biopsies from human livers during transplant surgery and supplied them to Cowart, who determined the levels of sphingosine kinase 1, the enzyme that makes S1P. They found double the normal amount of sphingosine kinase 1 in livers of obese people with non-alcoholic steatohepatitis. The team wanted more understanding of why S1P causes inflammation, but NASH has previously been difficult to mimic in the laboratory setting. They developed a new and highly improved preclinical model of NASH, wherein mice were fed on custom-designed diets of either high saturated fat or high unsaturated fat. Curiously, mice on each type of diet became obese, but only mice on the saturated fat diet developed inflammation and NASH-like pathology stemming from S1P. Taking the human and pre-clinical studies together, it's likely that saturated fat, but not unsaturated fat, raises S1P levels in obese people, and it's S1P that unleashes the inflammation that characterizes NASH. Performing lipid studies in the laboratory is not easy--most biochemistry is water-based, and fat and water don't easily mix. The group relied on the MUSC Sphingolipidomics Core laboratory, one of only a handful of such facilities in the country capable of developing the new methods needed to examine S1P for their study. "Without lipidomics, we never would have understood that saturated fats activate this pathway," says Cowart. The team is working to identify the S1P receptors responsible for inflammation in NASH, with the ultimate goal of designing treatments to prevent the need for a liver transplant in obese patients with NASH. Does this work support the idea that it's the type of fat, but not all fat, that leads to health problems? After all, mice fed a high unsaturated fat diet still became obese but were metabolically healthy. "Because the unsaturated fat diet didn't cause NASH, it may provide a clue as to what actually links obesity to disease," says Cowart. "Even if it's difficult to lose weight, dietary modifications might prevent some disease associated with obesity." Source: Medical University of South Carolina Posted in: Medical Science News | Medical Research News | Medical Condition News Comments (0) Download PDF Copy Suggested Reading Obesity drives shared genetic risk behind many chronic disease combinations Screen time may increase body fat in children Obesity drives one in ten infectious disease deaths Research shows the effect of losing weight in preventing multiple diseases Low-grade inflammation connects aging, obesity and cognitive impairment Breastfeeding and healthy infant diets may help lower obesity risk by age nine Eating melatonin-rich foods is linked to lower obesity and depression rates Addressing unsustainable food systems can deliver double benefits for health and climate Comments The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical. 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Saturated fat increases sphingosine-1-phosphate (S1P) levels in obese individuals, driving inflammation and progression of non-alcoholic steatohepatitis (NASH), unlike unsaturated fat.

5 bullets 4 citations (0 strong) 7 tags 5 clues 2 high-risk flags

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One-line Summary

Saturated fat increases sphingosine-1-phosphate (S1P) levels in obese individuals, driving inflammation and progression of non-alcoholic steatohepatitis (NASH), unlike unsaturated fat.

Decision Bullets

Scientific Summary: S1P synthesized via sphingosine kinase 1 is elevated by saturated fats and promotes liver inflammation driving NASH in obese patients.

View citation support (1)

The team is working to identify the S1P receptors responsible for inflammation in NASH, with the ultimate goal of designing treatments to prevent the need for a liver transplant in obese patients with NASH.

…heir study. "Without lipidomics, we never would have understood that saturated fats activate this pathway," says Cowart. The team is working to identify the S1P receptors responsible for inflammation in NASH, with the ultimate goal of designing treatments to prevent the need for a liver transplant in obese patients with NASH . Does this work support the idea that it's the type of fat, but not all fat, that leads to health problems? After all, …

Offsets: 5128–5334

Confidence: 76% Medium
Evidence Gaps: Precise identification of S1P receptors mediating inflammation remains incomplete, limiting targeted therapeutic design.

View citation support (1)

The team is working to identify the S1P receptors responsible for inflammation in NASH, with the ultimate goal of designing treatments to prevent the need for a liver transplant in obese patients with NASH.

…heir study. "Without lipidomics, we never would have understood that saturated fats activate this pathway," says Cowart. The team is working to identify the S1P receptors responsible for inflammation in NASH, with the ultimate goal of designing treatments to prevent the need for a liver transplant in obese patients with NASH . Does this work support the idea that it's the type of fat, but not all fat, that leads to health problems? After all, …

Offsets: 5128–5334

Confidence: 67% Medium
Medical Insights: Differentiating fat types in diet interventions may reduce NASH incidence despite persistent obesity.

View citation support (1)

"Because the unsaturated fat diet didn't cause NASH, it may provide a clue as to what actually links obesity to disease," says Cowart.

…s to health problems? After all, mice fed a high unsaturated fat diet still became obese but were metabolically healthy. "Because the unsaturated fat diet didn't cause NASH, it may provide a clue as to what actually links obesity to disease," says Cowart . "Even if it's difficult to lose weight, dietary modifications might prevent some disease associated with obesity." Sou…

Offsets: 5541–5675

Confidence: 73% Medium
Stakeholder Considerations: Patients, clinicians, and researchers should prioritize lipid type over weight alone in managing NASH risk.

View citation support (1)

No supporting quote found.

Confidence: 20% Weak
Next Steps: Focus on elucidating S1P receptor pathways and developing S1P-targeted therapies to prevent progression to liver transplant.

View citation support (1)

The team is working to identify the S1P receptors responsible for inflammation in NASH, with the ultimate goal of designing treatments to prevent the need for a liver transplant in obese patients with NASH.

…heir study. "Without lipidomics, we never would have understood that saturated fats activate this pathway," says Cowart. The team is working to identify the S1P receptors responsible for inflammation in NASH, with the ultimate goal of designing treatments to prevent the need for a liver transplant in obese patients with NASH . Does this work support the idea that it's the type of fat, but not all fat, that leads to health problems? After all, …

Offsets: 5128–5334

Confidence: 69% Medium

Mind Map

mindmap
  root((NASH in Obese))
    Causes
      Dietary Fat
        Saturated Fat --> Increases S1P
        Unsaturated Fat --> Obesity without NASH
    Mechanism
      Sphingosine Kinase 1 --> Produces S1P
      S1P --> Inflammation --> NASH Progression
    Evidence
      Human Liver Biopsies --> Elevated kinase in obese NASH
      Mouse Models --> Saturated fat diet induces NASH
    Gaps
      Unknown S1P Receptors
    Outcomes
      NASH --> Cirrhosis & Liver Cancer
      Need for Liver Transplant
    Future Directions
      Identify S1P Receptors
      Develop Targeted Therapies
      Dietary Modification Emphasis

#	Bullet	Supporting Quote	Level
1	Scientific Summary: S1P synthesized via sphingosine kinase 1 is elevated by saturated fats and promotes liver inflammation driving NASH in obese patients.	"The team is working to identify the S1P receptors responsible for inflammation in NASH, with the ultimate goal of designing treatments to prevent the need for a liver transplant in obese patients with NASH."	Medium
2	Evidence Gaps: Precise identification of S1P receptors mediating inflammation remains incomplete, limiting targeted therapeutic design.	"The team is working to identify the S1P receptors responsible for inflammation in NASH, with the ultimate goal of designing treatments to prevent the need for a liver transplant in obese patients with NASH."	Medium
3	Medical Insights: Differentiating fat types in diet interventions may reduce NASH incidence despite persistent obesity.	""Because the unsaturated fat diet didn't cause NASH, it may provide a clue as to what actually links obesity to disease," says Cowart."	Medium
4	Stakeholder Considerations: Patients, clinicians, and researchers should prioritize lipid type over weight alone in managing NASH risk.	—	None
5	Next Steps: Focus on elucidating S1P receptor pathways and developing S1P-targeted therapies to prevent progression to liver transplant.	"The team is working to identify the S1P receptors responsible for inflammation in NASH, with the ultimate goal of designing treatments to prevent the need for a liver transplant in obese patients with NASH."	Medium

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Saturated fat increases sphingosine-1-phosphate (S1P) levels in obese individuals, driving inflammation and progression of non-alcoholic steatohepatitis (NASH), unlike unsaturated fat.

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