Interested in lipids? Join us @ the 2026 FASEB Lipid Droplet: From Mechanisms to Disease Conference (July 26-30, Scottsdale, AZ). Registration is now open!
events.faseb.org/event/Lipid-...
We are co-locating with the FASEB Phospholipids SRC! Register for one to enjoy BOTH meetings!
Mouse studies highlight the therapeutic potential of existing and emerging strategies to manipulate the bile acid pool and to regulate dietary fat absorption across a spectrum of conditions—from malabsorptive disorders to cardiometabolic diseases www.cell.com/cell-metabol...
Thank you to @cp-cellmetabolism.bsky.social @cellpress.bsky.social for the opportunity to share our work!
This work was made possible by funding from the #NIH (NHLBI, NIDDK), @ahascience.bsky.social, @uclahealth.org, @domucla.bsky.social, @damonrunyon.org, @themarkfdn.bsky.social, #ADA, #CTSI
🎉 Our findings reveal exciting therapeutic potential: targeting bile acids could offer novel treatments for obesity, MASLD, and metabolic disorders. 🎉
Next, we used AAV-CRISPR to disrupt CYP8B1 (⬇️CA), CYP2C70 (⬆️CDCA, ⬇️MCAs), and CYP2A12 (⬆️DCA). Only CYP8B1 disruption replicated selective absorption, proving CA drives🚗 this effect. ⛑️Rescuing CYP7A1-deficient mice with dietary bile acids confirmed that strong detergent bile acids restore absorption.
🥁The mechanism: physio-chemical properties of both fats and bile acids matter, ‼️ but not all bile acids are equal ‼️ Cholic acid (CA) selectively solubilizes fats, while other bile acids did not, identifying CA as the 🔑 key mediator of selective fat absorption.
We then measured individual fatty acid absorption. Reduced bile acids decreased saturated fat absorption, but adding double bonds reversed this. MUFAs and PUFAs were nearly fully absorbed! 🤯 Orlistat reduced all fatty acids equally, revealing 2️⃣ distinct absorption mechanisms.
Liver lipidomics 👩🔬🧑💻 revealed both models reduced steatosis, but with key differences: CYP7A1 loss increased PUFA-containing TAGs while most TAG species decreased. Orlistat decreased PUFAs, triggering compensatory SREBP1c-dependent lipogenesis.
🤔 Why no increased food intake? CYP7A1-deficient mice showed elevated GLP-1 and PYY secretion (unlike orlistat-treated mice). This GLP-1 increase required GPR120, suggesting fatty acids reach the distal gut to activate this receptor when bile acids are reduced.
Next, we compared decreasing bile acids to lipase inhibition (orlistat). Despite increased 💩 fecal output, orlistat didn't prevent obesity: mice ate more 😋. Critically, CYP7A1-deficient mice didn't increase food intake, a key finding since hyperphagia typically follows reduced absorption.
Using AAV-CRISPR to target liver bile acid enzymes 🧬, we knocked down CYP7A1 (rate-limiting enzyme in bile acid synthesis) and protected mice 🐭 from diet-induced obesity 🍔. This increased fecal calories, indicating reduced absorption, with no changes in energy expenditure or food intake.
🚨Our new Cell Metabolism paper is PUBLISHED!🚨By targeting bile acids, we can promote selective fatty acid absorption to improve metabolic health. 🧬🍔 Studies co-led by UCLA STAR fellow Alvin Chan, postdoc Kelsey Jarrett, and grad student Rochelle Lai.
Excited to present some of our recent work at UC Berkeley today! @natureatcal.bsky.social
Super proud of our post-doc Heidi Schmidt who was selected as the winner of the Shobha Ghosh Investigator in Training Award at Vascular Discoveries! @ahascience.bsky.social
Mark your calendars & repost! Join us for the 2026 FASEB Lipid Droplets Conference!
July 26-30, 2026 in beautiful Scottsdale, Arizona.
Best of all: The FASEB Lipid Droplet meeting is co-locating with the FASEB Phospholipid meeting. Two wonderful lipid communities brought together!
Excited to see my mentor’s achievements highlighted!
At the suggestion of @conway-group.bsky.social I've created a starter pack to connect UCLA-based researchers on bluesky. If you want to be added, please let me know! go.bsky.app/A19PmEa
