Scientific Abstract

This conversation with Dr. Tore Bengtsson, professor of physiology at Stockholm University, explores how β-adrenergic receptor signaling can be reimagined to address metabolic disease, muscle physiology, and energy balance. Dr. Bengtsson’s research spans sympathetic nervous system signaling, brown adipose tissue biology, and skeletal muscle metabolism—fields deeply connected to obesity, type 2 diabetes, and metabolic health.

A central theme of the discussion is the pharmacology of the β₂-adrenergic receptor, a GPCR traditionally associated with bronchodilation but increasingly recognized for its broader physiological roles. Dr. Bengtsson describes how classical β₂ agonists stimulate muscle growth and metabolic changes but are limited by receptor desensitization. His work focuses on developing novel β₂-adrenergic ligands that selectively engage signaling pathways without triggering rapid desensitization, enabling sustained metabolic effects.

The conversation also examines how GPCR signaling is far more complex than a single downstream pathway. Instead, receptors integrate multiple signaling outputs, temporal dynamics, and interactions with other pathways to shape physiological outcomes. Dr. Bengtsson discusses how understanding this signaling complexity opens opportunities to design drugs that promote beneficial metabolic responses such as muscle growth and increased energy expenditure.

Listeners gain insight into how basic GPCR pharmacology can translate into therapeutic strategies targeting metabolism, aging, and metabolic disease.

About the Guest

Dr. Tore Bengtsson is a professor of physiology at Stockholm University whose research focuses on sympathetic nervous system signaling, metabolic regulation, and skeletal muscle physiology. His work investigates how β-adrenergic receptors regulate energy metabolism, muscle growth, and glucose homeostasis.

Dr. Bengtsson began his research career studying brown adipose tissue under the mentorship of Dr. Barbara Cannon and Dr. Jan Nedergaard, pioneers in thermogenesis research. His laboratory now explores how β₂-adrenergic receptor signaling can be manipulated to influence metabolism and muscle physiology. He is also an entrepreneur and founder of biotechnology companies translating GPCR pharmacology into therapeutic development.

Scientific Themes of the Conversation

• β-adrenergic receptor pharmacology and signaling bias

• Sympathetic nervous system control of metabolism

• Brown adipose tissue and thermogenesis

• Skeletal muscle metabolism and glucose homeostasis

• GPCR signaling complexity and pathway selectivity

• Translating receptor pharmacology into metabolic therapeutics

Key Insights from the Conversation

A Childhood Physiological Experiment Sparked a Scientific Career

Dr. Bengtsson recounts a formative experience when his father pushed him into icy water as a child to demonstrate survival in cold conditions. The intense physiological response—an adrenaline surge and rapid adaptation to cold—sparked his lifelong fascination with sympathetic nervous system signaling and stress physiology.

Stress Is Not Always Negative

A recurring theme in the discussion is that physiological stress is often misunderstood. Short bursts of stress—whether exercise, cold exposure, or sympathetic activation—can trigger adaptive responses that improve metabolic function and resilience.

Muscle Is Central to Metabolic Health

While brown fat has received considerable attention, Dr. Bengtsson emphasizes the dominant role of skeletal muscle in metabolic regulation. Approximately 75% of glucose disposal occurs in muscle, making muscle physiology central to metabolic diseases such as type 2 diabetes.

Classical β₂ Agonists Have a Fundamental Limitation

Traditional β₂-adrenergic agonists can stimulate muscle growth and fat loss but lose effectiveness over time due to receptor desensitization. This pharmacological limitation prevents their long-term use for metabolic therapies.

GPCRs Do Not Produce a Single Signal

Dr. Bengtsson highlights that GPCR signaling is inherently multidimensional. Activation of a receptor can generate multiple signaling pathways, and different ligands can bias signaling toward specific outcomes. Understanding this complexity is essential for modern drug discovery.

Absence of a Signal Can Be a Discovery

One of Dr. Bengtsson’s key scientific breakthroughs came from an unexpected experimental result: glucose uptake without detectable cAMP signaling. Rather than dismissing the result as an error, this observation led to the realization that β₂ signaling could be separated into distinct pathways.

Scientific Discovery Requires Intellectual Independence

Dr. Bengtsson advises young scientists to shift from passively following instructions to actively questioning experiments and interpretations. True scientific thinking begins when researchers take intellectual ownership of the questions they pursue.

Episode Timeline

00:00 Introduction and research focus of Dr. Bengtsson

03:00 A childhood experiment that sparked interest in physiology

07:00 Cold exposure, sympathetic signaling, and brown fat research

10:00 β₂-adrenergic receptors and muscle physiology

15:00 Exercise, metabolism, and pharmacological modulation of muscle growth

17:30 Early research on brown adipose tissue and thermogenesis

22:30 Translating academic discoveries into biotech companies

25:00 GPCR signaling complexity and biased signaling

36:00 A key experimental observation leading to a new drug concept

38:30 Advice for young scientists and intellectual independence

Selected Quotes

Full Transcript

(Formatted for readability — full transcript preserved)

Yamina Berchiche:

Hello, everyone. This is Yamina from Dr. GPCR. And today I'm very excited to have with me Dr. Tore Bengtsson.

Dr. Bengtsson:

Tore Bengtsson. And you got it right.

Yamina Berchiche:

I'm happy to have you on. For those who don't know, we've been chasing each other and postponing this conversation several times. I'm very excited that we're finally able to do it today.

Dr. Bengtsson:

Thank you. I'm very happy to be here.

Yamina Berchiche:

Let's start at the beginning. Could you introduce yourself and tell us about your research?

Dr. Bengtsson:

I'm a professor in physiology at Stockholm University. I've been working with pre-diabetes, type 2 diabetes, obesity, and the mechanisms behind these diseases for about 25 years. I'm especially interested in β-adrenergic receptors because I believe they regulate far more physiological processes than people typically assume.

I'm also an entrepreneur. I've started several companies. One is Sigrid Therapeutics, which focuses on digestion and metabolic regulation. Another company, Atrogi, is based on our research on β₂-adrenergic receptors and the development of new drugs.

We’ve already completed Phase I clinical trials and are preparing for Phase II.

Yamina Berchiche:

If you were not a scientist, what would you be doing?

Dr. Bengtsson:

I think I might have been a historian or a writer. I like storytelling. I'm very interested in Viking runes and ancient rune stones in Scandinavia. I can actually read runic inscriptions, and I find it fascinating to interpret what these stones tell us about history.

Yamina Berchiche:

How did you become a scientist?

Dr. Bengtsson:

I'll tell you a story I don't share very often.

When I was about ten years old, I lived on an island in the Stockholm archipelago. My father and I went ice skating frequently during the winter. One summer he asked me: “What happens if you fall through the ice?”

I said I didn't know.

He replied: “We should test it.”

Months later, during winter, he cut a hole in the ice. I asked what he was doing. He said he was catching a big fish. Suddenly he pushed me into the icy water.

I went under, looked up at the hole in the ice, and quickly swam out. I remember the intense adrenaline surge. My body reacted instantly. I wasn't even cold at first.

Walking home later I started to freeze, but in that moment I experienced a powerful physiological response.

That event sparked my lifelong fascination with sympathetic nervous system activation.

Yamina Berchiche:

So your father pushed you into science quite literally.

Dr. Bengtsson:

Yes — and into physiology.

Yamina Berchiche:

And that connects directly to your later work on brown fat and sympathetic signaling.

Dr. Bengtsson:

Exactly. I've spent many years studying brown adipose tissue and how sympathetic activation stimulates thermogenesis. Later I became increasingly interested in skeletal muscle metabolism and how β₂-adrenergic signaling affects muscle growth and glucose metabolism.

Yamina Berchiche:

Could you talk about how β₂-adrenergic signaling relates to muscle growth?

Dr. Bengtsson:

For many years it's been known that β₂ agonists can stimulate muscle growth and reduce fat. This has been observed in athletes and even in livestock production.

But traditional β₂ agonists lose effectiveness over time because the receptor becomes desensitized. The body adapts, requiring higher doses. That makes them unsuitable as long-term therapeutic drugs.

So about 15–20 years ago I began working on the idea that we need a new type of β₂ agonist—one that activates the receptor differently and avoids desensitization.

That’s what we’ve now achieved with new compounds that stimulate the receptor in a novel way.

Yamina Berchiche:

You mentioned something very important earlier: GPCRs don’t produce a single signal.

Dr. Bengtsson:

Yes. Traditionally people thought receptor activation leads to one downstream pathway. But GPCRs activate multiple signaling pathways simultaneously.

Different ligands can bias signaling toward different pathways. That means we can design compounds that favor beneficial physiological responses while avoiding unwanted effects.

That is exactly what makes GPCR pharmacology so fascinating and powerful.

Yamina Berchiche:

You mentioned an important experimental moment that led to your drug concept.

Dr. Bengtsson:

Yes. A doctoral student ran an experiment measuring glucose uptake. The compound produced strong glucose uptake but almost no cAMP signaling.

She thought the experiment had failed.

But I realized this might be something important: glucose uptake without cAMP.

And that turned out to be correct. That observation opened the door to separating signaling pathways and designing new β₂ ligands.

Yamina Berchiche:

What advice would you give to young scientists?

Dr. Bengtsson:

Young scientists often follow instructions without asking why.

Real science begins when you take control of the question. You must move from being told what to do to thinking independently.

You have to be in the driver's seat of your own thinking.

Yamina Berchiche:

That’s a powerful message.

Dr. Bengtsson:

And another lesson I learned from my wife: success often depends not just on knowledge but on understanding how other people think.

Science is not just experiments. It's communication, persuasion, and collaboration.

Yamina Berchiche:

Dr. Bengtsson, thank you very much for the conversation.

Dr. Bengtsson:

Thank you. This was great.

Yamina Berchiche:

Bye.

Dr. Bengtsson:

Bye-bye.