Related Experiment Videos
Systemic short-chain fatty acids rapidly alter gastrointestinal structure, function, and expression of early response
1Department of Food Science and Human Nutrition, University of Illinois, Urbana 21801, USA.
Abstract:
Luminal and systemic short chain fatty acids (SCFA) stimulate mucosal proliferation but the mechanism(s) is unclear. This study examined acute effects of systemic SCFAs on gastrointestinal structure and function and signals potentially mediating SCFA-induced mucosal proliferation. Male Sprague-Dawley rats (246+/-2 g) received nutrients as either standard total parenteral nutrition (TPN) or an isoenergetic, isonitrogenous formulation containing SCFAs (TPN + SCFA). Animals were randomized to one of five treatments: standard TPN for 72 hr, TPN + SCFA for 72 hr, or standard TPN followed by TPN + SCFA for the final 6, 12, and 24 hr. SCFAs reduced (P < 0.003) ileal protein within 6 hr. Jejunal GLUT2 expression was increased (P=0.0001) in all SCFA groups and ileal GLUT2 protein in the 6-, 12-, and 24-hr SCFA groups (P < 0.05). SCFAs increased (P < 0.003) ileal proglucagon abundance following 6, 12, and 24 hr, and plasma GLP-2 concentration following 12 hr (P < 0.03). Jejunal c-myc expression was increased (P < 0.001) following 6, 12, and 24 hr of SCFAs. SCFAs increased ileal c-myc, c-jun, and c-fos expression following 24 hr (P < 0.02), 12 hr (P < 0.05) and 6, 12, and 24 hr (P=0.0001), respectively. In conclusion, systemic SCFAs increase plasma GLP-2 and ileal proglucagon mRNA, GLUT2 expression and protein, and c-myc, c-jun, and c-fos expression.
Insights
Systemic short-chain fatty acids (SCFAs) promote gastrointestinal mucosal proliferation by increasing GLUT2, proglucagon, and GLP-2. These SCFAs also upregulate key genes like c-myc, c-jun, and c-fos, crucial for cell growth.
Area of Science:
- Gastroenterology
- Molecular Biology
- Nutritional Science
Background:
- Short-chain fatty acids (SCFAs) are known to stimulate mucosal proliferation, but the underlying mechanisms remain unclear.
- Understanding how SCFAs influence gastrointestinal structure and function is crucial for therapeutic applications.
Purpose of the Study:
- To investigate the acute effects of systemic SCFAs on gastrointestinal structure and function.
- To identify signaling pathways mediating SCFA-induced mucosal proliferation.
Main Methods:
- Male Sprague-Dawley rats were administered standard total parenteral nutrition (TPN) or TPN supplemented with SCFAs (TPN + SCFA).
- Animals received treatments for varying durations (6, 12, 24, or 72 hours) to assess acute responses.
- Key molecular markers including GLUT2, proglucagon, GLP-2, c-myc, c-jun, and c-fos were quantified.
Main Results:
- Systemic SCFAs rapidly reduced ileal protein and increased jejunal GLUT2 expression within 6 hours.
- SCFAs elevated ileal proglucagon mRNA and plasma GLP-2 concentrations.
- Increased expression of jejunal c-myc, and ileal c-myc, c-jun, and c-fos was observed following SCFA administration.
Conclusions:
- Systemic SCFAs enhance gastrointestinal mucosal proliferation through increased GLP-2 and proglucagon.
- SCFAs modulate GLUT2 expression and activate key genes (c-myc, c-jun, c-fos) involved in cell proliferation.
- These findings elucidate critical molecular mechanisms underlying SCFA-mediated mucosal growth.