The Metabolic Classroom with Dr. Ben Bikman

Episode: How Bile Controls Insulin, GLP-1, and Fat Burning

Date: February 23, 2026
Host: Dr. Ben Bikman (Metabolic Scientist & Professor of Cell Biology)

Episode Overview

In this episode of The Metabolic Classroom, Dr. Ben Bikman dives deep into the science of bile: its production, roles beyond just fat digestion, and its critical influence on overall metabolic health. Dr. Bikman reveals how bile acids function as signaling molecules—essentially acting as hormones—that affect insulin sensitivity, GLP-1 levels, fat burning, inflammation, and more. He discusses the implications of gallbladder removal, the practicalities and evidence surrounding bile supplements, and why understanding bile’s signaling roles may help us address obesity, diabetes, and metabolic dysfunction.

Key Discussion Points & Insights

1. What is Bile and How is it Made?

(02:26 – 05:20)

• Bile is produced by liver cells (hepatocytes), with an adult liver making ~400-800 mL per day—about 95% water, plus bile acids, phospholipids, cholesterol, and bilirubin.
• Bile acids are synthesized from cholesterol (“bile acid synthesis is actually the primary route through which the body eliminates cholesterol”).
• The main bile acids: cholic acid and chenodeoxycholic acid; these are conjugated with glycine or taurine to be more effective in the gut.
• Bile can be stored and concentrated (5-10x) in the gallbladder before release.

Quote:

"When you eat a meal containing fat, a hormone called cholecystokinin or CCK signals the gallbladder to contract and release all of that concentrated bile into the intestine."
— Dr. Ben Bikman (05:06)

2. Bile’s Classic Role in Digestion

(05:21 – 06:36)

• Bile emulsifies dietary fats (“acts as a biological detergent”), breaking them into micelles for digestion by lipases.
• Without bile, fat digestion, absorption, and absorption of vitamins A, D, E, and K are impaired.

3. The Recycling of Bile – Enterohepatic Circulation

(06:37 – 08:06)

• 95% of bile acids are reabsorbed in the ileum (end of the small intestine), then return to the liver through portal blood.
• This recycling, called enterohepatic circulation, happens 6-12 times daily, ensuring a small bile acid pool (~2-4 grams) is used efficiently.

Quote:

“The total bile acid pool is only about 2 to 4 grams, but it cycles 6 to 12 times per day.”
— Dr. Ben Bikman (07:24)

4. Bile Acids as Metabolic Signaling Molecules

(08:07 – 10:49)

• Bile acids activate specific receptors throughout the body: FXR and TGR5.
• Function not just in digestion, but are “bona fide hormones” affecting gene expression, insulin sensitivity, fat metabolism, and inflammation.

Deep Dive: Bile Acid Receptors

1. FXR (Farnesoid X Receptor)

(08:50 – 10:49)

• Location: Nucleus of liver and intestinal cells.
• Activation results:
  • Decreases new fat creation in liver (reducing liver fat).
  • Improves insulin sensitivity.
  • Promotes glycogen synthesis.
  • Reduces excessive liver glucose production (helpful for type 2 diabetes).
  • Stimulates gut hormone FGF19, which further dampens liver glucose output and downregulates bile acid production.

Quote:

"Every time bile acids are reabsorbed and activate FXR, it's like a metabolic reset of sorts."
— Dr. Ben Bikman (10:00)

2. TGR5 (G Protein-Coupled Bile Acid Receptor)

(12:47 – 16:55)

• Location: Cell membranes in brown fat, muscle, gut, and immune cells.
• Key functions:
  • In Brown Fat/Muscle: Increases energy expenditure (“increasing mitochondrial activity and more thermogenesis”).
  • In Gut (L cells): Increases GLP-1 secretion—endogenous activation of the body’s own weight-loss hormone, central in diabetes/obesity drugs.
  • In Immune Cells: Reduces inflammation by lowering pro-inflammatory cytokines.

Quote:

“So bile acids through TGR5 are your body’s own endogenous stimulators of GLP-1 release, a built-in mechanism for what these drugs are attempting to do pharmacologically.”
— Dr. Ben Bikman (14:23)

Bile’s Effects on Fat Cells and Metabolism

(16:56 – 19:01)

• Both FXR and TGR5 are in fat tissue; their activation:
  • Influences how new fat cells are generated and how they handle fat.
  • Reduces inflammation within fat.
  • Improves the secretion of beneficial adipokines (e.g., leptin, adiponectin).
  • Supports smaller, healthier adipocytes (fat cells).
  • Increases mitochondrial activity and number in brown fat, boosting energy expenditure.

Quote:

“Bile acid signaling through both FXR and TGR5 represents a pathway for restoring healthier fat cell function. It reduces inflammation, it improves the secretion of adipokines... and it supports a better lipid overall cycle and balance.”
— Dr. Ben Bikman (18:28)

Bile Acid Medications and Clinical Implications

(19:02 – 20:37)

• Bile acid sequestrants (e.g., Colesevelam): Originally prescribed to lower LDL cholesterol, but surprisingly effective at improving blood glucose in type 2 diabetes (via shifting bile acid signaling, not cholesterol absorption).
• “The details of signaling matter as much as the quantity.”

Gallbladder Removal: Metabolic Implications

(22:05 – 23:37)

• After cholecystectomy (gallbladder removal):
  • Bile flows continuously into the small intestine—no longer concentrated or timed with meals.
  • The “enterohepatic circulation speeds up,” but the bile pool shrinks by ~50%.
  • Some compensation, but imperfect.
• Epidemiological studies link cholecystectomy to higher rates of metabolic syndrome, fatty liver, and abnormal glucose regulation.
• The gallbladder is more than a storage bag—think of it as “a metabolic pacemaker of sorts.”

Quote:

“We really do need to think of the gallbladder as a metabolic pacemaker of sorts, and its loss … does have consequences that go beyond digestion.”
— Dr. Ben Bikman (22:55)

Bile Acid Supplements: Do They Work?

(23:38 – 26:30)

• Ox bile: Widely used after gallbladder removal to aid fat digestion. Anecdotally helpful, but “large scale rigorous trials … are pretty limited.”
• TUDCA (tauroursodeoxycholic acid):
  • Acts as a chemical chaperone, reduces cellular stress, and has anti-inflammatory effects.
  • Human study: 1.75g per day for 4 weeks improved insulin sensitivity by 30% (comparable to weight loss or metformin).
  • In animal studies: reduces fat, lowers insulin, protects pancreatic beta cells.
  • Safe so far, worth discussing with clinicians for those with insulin resistance or after gallbladder removal, but not recommended universally (more research needed).

Quote:

“The mechanistic rationale is compelling, the safety profile is strong, and for individuals with insulin resistance, particularly those without a gallbladder, then I think it would be worth exploring implementing some TUDCA.”
— Dr. Ben Bikman (25:45)

Conclusion & Takeaways

(26:31 – 27:49)

• Bile acids aren’t just digestive aids; they are influential signaling molecules affecting metabolism body-wide.
• Through FXR and TGR5, bile acids powerfully regulate:
  • Liver fat accumulation
  • Glucose production
  • Insulin sensitivity
  • GLP-1 secretion
  • Inflammation
  • Mitochondrial biogenesis and energy expenditure
• The gallbladder’s role in timing and concentrating bile is central for optimal metabolic signaling.
• Loss of the gallbladder carries metabolic consequences, but adaptation and some supplements may help mitigate these effects.
• “More knowledge, better health.”

Notable Quote:

“Bile acids are among the most important metabolic signaling molecules in the body, among the most important, and I would say, among the most overlooked.”
— Dr. Ben Bikman (26:42)

Timestamps of Important Segments

| Timestamp | Segment | |-----------|--------------------------------------------------------------------------| | 02:26 | What is bile, how is it made, and what’s in it? | | 05:21 | Bile’s classic role in digestion | | 06:37 | The recycling (enterohepatic circulation) of bile | | 08:50 | FXR receptor and its effects on metabolism | | 12:47 | TGR5 receptor in brown fat, muscle, gut, and immune cells | | 16:56 | Bile acids and adipose tissue (fat cell metabolism and inflammation) | | 19:02 | Clinical drugs: bile acid sequestrants and unexpected metabolic effects | | 22:05 | Gallbladder removal and its metabolic consequences | | 23:38 | Bile acid supplements: ox bile and TUDCA effects and evidence | | 26:31 | Final takeaways: why bile is central to metabolism |

Memorable Highlights

• “Bile acids are your body’s own endogenous stimulators of GLP-1 release—a built-in mechanism for what these drugs are attempting to do pharmacologically.” (14:23)
• “A fatty liver is one of the most potent drivers of insulin resistance. It actually ends up being both cause and consequence of insulin resistance.” (09:51)
• “We really do need to think of the gallbladder as a metabolic pacemaker.” (22:55)

For practical application and further learning, Dr. Bikman emphasizes sharing these insights with friends and clinicians, especially when facing gallbladder issues or metabolic disease.