Unexpected findings that brown fat is a metabolic regulator as well as a thermogenic generator are moving diabetes research in unexpected directions. All because a young researcher spent his first winter at the University of Michigan wondering how humans had evolved to survive the frigid winters in Ann Arbor.

“When I moved to Michigan as part of my PhD to study zebrafish development, I had never experienced such cold temperatures in my life,” said Shingo Kajimura, PhD, Professor of Endocrinology, Diabetes, and Medicine, Harvard Medical School, and Beth Israel Deaconess Medical Center. “This made me think about how animals can adapt to prolonged severe cold weather, and one day I heard about brown fat, which was thought to be a heat organ for animals to maintain body temperature during the winter. Large amounts of mitochondria give it its brown color, so I thought I could study brown fat as a unique model of mitochondrial biology.”

Dr. Kajimura recounted the twisting journey that began that first Michigan winter during his Outstanding Scientific Achievement Award lecture, “An Unexpected Journey into Brown Fat Research for Metabolic Health” on Monday morning, June 23, at the 85^th Scientific Sessions.

What began as curiosity about the mechanisms of thermogenesis became the discovery that brown fat is a potent metabolic regulator that can control insulin and glucose levels independent of thermogenesis and independent of the canonical uncoupling protein 1 (UPC1) pathway, he explained during the session, National Scientific & Health Care Achievement Awards Presentation and Outstanding Scientific Achievement Award Lecture.

Brown adipose tissue is the most mitochondria-rich tissue in the human body, Dr. Kajiura explained. Unlike white adipocytes, which have few mitochondria, have low fuel oxidation, and store energy as lipids, brown adipocytes are rich in mitochondria and exhibit high fuel oxidation to dissipate energy as heat.

Most, perhaps all, warm-bodied animals have brown fat, from human infants, who are born with brown fat to generate heat until their muscles develop to support shivering, to hibernating mammals and warm-bodied fish such as swordfish and blue fin tuna.

Adult humans also have deposits of brown fat and beige fat, which can be recruited as brown fat as needed. Brown fat UPC1 was thought to maintain metabolic health through UPC1 to regulate energy expenditures, body weight, glucose homeostasis, insulin sensitivity, and more.

Working with UCP1 knockout mice, Dr. Kajimura’s lab found that brown fat ablation causes insulin resistance independent of body weight even though the mice were not diabetic.

“I did not intend to study metabolism in diabetes at the time, but this observation was too puzzling to ignore,” Dr. Kajimura said. “This observation forced me to think that maybe brown fat is doing something different from UPC1. It was a radical idea at the time, but we decided to test it.”

A novel mouse model provided direct evidence of UCP1-independent thermogenesis and effects on body weight, and glucose homeostasis. Brown fat regulates thermogenesis via UCP1 and independent of UPC1. Other UPC1-independent pathways regulate metabolic flux and tissue homeostasis.

“Our data suggest this UPC1-independent pathway is important, particularly in the context of body weight maintenance,” Dr. Kajimura said. “This may lead to new opportunities for maintaining energy expenditure and metabolic health in a post-GLP-1 (glucagon-like peptide-1) era. For the next 5–10 years, there will be many important discoveries in this area which will open many new opportunities—and questions.”

K.M. Venkat Narayan, MD, MBA, MSc, FRCPI, Executive Director of the Emory Global Diabetes Research Center, delivered the second special lecture of the morning, “Global Diabetes—Rapidly Changing Landscape and a Rising Tide of Opportunities,” describing the work that led to his 2025 International Service in the Cause of Diabetes Award.