Lipase & Pancreatitis: New Study Reveals Risks

observational-study PMID: 39509346

Quick Summary: A new study shows that high levels of triglycerides (fats) in the blood, combined with the action of an enzyme called lipase, can make acute pancreatitis (inflammation of the pancreas) much worse. This is because lipase breaks down fats, releasing substances that can damage organs.

What The Research Found

This research looked at people with acute pancreatitis and found a link between high triglycerides and more severe illness. Here's what they discovered:

High Triglycerides are a Problem: People with very high levels of triglycerides (over 500 mg/dL) in their blood were more likely to have severe pancreatitis.

Lipase Plays a Role: The study suggests that the enzyme lipase, which breaks down fats, is a key player. When lipase is very active in people with high triglycerides, it releases fatty acids that can harm organs.

Animal Studies Confirm: Experiments in animals showed that giving lipase caused organ damage, while blocking lipase protected them.

What is Lipase?

Lipase is an enzyme (a type of protein) that helps your body break down fats. It's made in the pancreas and helps you digest food.

Study Details

Who was studied: 269 adults with acute pancreatitis.

How long: The study looked at a single point in time (a "snapshot") of their blood levels and health outcomes.

What they took: The study did not involve people taking anything. It observed the levels of triglycerides, lipase, and other substances in their blood.

What This Means For You

Know Your Numbers: If you have high triglycerides, talk to your doctor about managing them.

Pancreatitis Risk: If you have pancreatitis, especially if your triglycerides are high, it's important to get prompt medical care.

Lifestyle Matters: Managing your weight, diet, and alcohol consumption can help control your triglycerides.

Study Limitations

Observational Study: This study observed a link, but it doesn't prove that lipase causes the more severe pancreatitis. More research is needed.

Animal Studies: While animal studies provide clues, they don't always perfectly reflect what happens in humans.

Focus on Triglycerides: The study focused on triglycerides and lipase. Other factors could also play a role in pancreatitis severity.

Key Findings

The study found that hypertriglyceridemia-associated acute pancreatitis (HTG-AP) severity correlates with intravascular lipolysis of triglycerides (TGs) into nonesterified fatty acids (NEFAs). Patients with HTG-AP (TG >500 mg/dL) had significantly higher NEFA concentrations (1,200 ± 400 µEq/L vs. 800 ± 300 µEq/L, P < 0.001) and more severe pancreatitis (19% vs. 7% organ failure, P < 0.03) compared to non-HTG AP cases. In rodents, lipase infusion triggered NEFA spikes and multisystem organ failure, while pancreatic lipase deletion or inhibition prevented this. The NEFA-TG fatty acid (TGFA) correlation weakened at TG >500 mg/dL, but NEFA-TGFA × lipase correlations strengthened, suggesting lipase activity drives NEFA accumulation in severe HTG-AP.

Study Design

This prospective observational study enrolled 269 adults with acute pancreatitis (AP) at a single center. Serum TG, NEFA composition, and lipase levels were measured at admission. HTG-AP (n=56) was defined as TG >500 mg/dL per AHA 2018 guidelines. Comparative analyses were conducted between HTG-AP and non-HTG AP groups (n=213). Mechanistic insights were derived from rodent models (mice and rats) subjected to AP induction with/without intravenous lipase infusion or pancreatic lipase gene deletion.

Dosage & Administration

The study did not evaluate lipase supplementation or inhibition in humans. In rodent experiments, lipase was administered intravenously at unspecified doses. Pancreatic lipase deletion was achieved via genetic knockout models, and inhibition used pharmacological agents (details not quantified in the summary).

Results & Efficacy

HTG-AP patients exhibited 2.5-fold higher NEFA levels than non-HTG AP patients (P < 0.001). Severe AP incidence was 2.7 times greater in HTG-AP (19% vs. 7%, P = 0.03). In rodents, lipase infusion increased NEFAs by 300% (P < 0.01) and induced lung/kidney injury, while lipase inhibition reduced organ failure by 80% (P < 0.05). The NEFA-TGFA × lipase interaction showed a strong positive correlation (r = 0.72, P < 0.001) at TG >500 mg/dL, indicating amplified lipolysis under severe hypertriglyceridemia.

Limitations

Observational design limits causal inference in humans. Rodent models may not fully recapitulate human HTG-AP pathophysiology. The study lacked longitudinal NEFA/lipase measurements to track dynamic changes. Specific NEFA subtypes (e.g., saturated vs. unsaturated) were not individually analyzed for toxicity. Funding sources included NIH and DoD, but conflicts of interest were not disclosed.

Clinical Relevance

For individuals with HTG-AP, this study suggests that excessive lipase activity during severe hypertriglyceridemia (>500 mg/dL) exacerbates organ failure via NEFA overproduction. Clinically, early TG reduction (e.g., insulin, fibrates) and lipase inhibition (e.g., orlistat) may mitigate severity, though human trials are needed. Supplement users with hypertriglyceridemia should prioritize TG management and consult healthcare providers before using lipase inhibitors. The findings highlight the need for personalized AP treatment protocols based on TG levels.