A team led by scientists at The Scripps Research Institute have discovered a direct link between insulin — a hormone long associated with metabolism and metabolic disorders such as diabetes — and core body temperature.
While much research has been conducted on insulin since its discovery in the 1920’s, this is the first time the hormone has been connected to the fundamental process of temperature regulation.
The scientists found that when insulin was injected directly into a specific area of the brain in rodents, core body temperature rose, metabolism increased, and brown adipose (fat) tissue was activated to release heat. The research team also found that these effects were dose-dependent — up to a point, the more insulin, the more these metabolic measures rose.
“Scientists have known for many years that insulin is involved in glucose regulation in tissues outside the brain,” said Scripps Research neurobiologist Manuel Sanchez-Alavez, first author of the new paper. “The connection to temperature regulation in the brain is new.”
In addition to suggesting a fresh perspective on diseases such as diabetes that involve the disruption of insulin pathways, the study adds to our understanding of core body temperature — the temperature of those parts of the body containing vital organs, namely the trunk and the head. Normally, core body temperature stays within a narrow range so that key enzymatic reactions can occur. When core body temperature goes outside this range for prolonged periods — higher as in fever, or lower as in hypothermia — the result is harm to the body.
More modest variations in core body temperature are associated with our daily 24-hour sleep-wake cycle, the female monthly hormonal cycle, and, intriguingly, the effects of severe calorie restriction.
“Our paper highlights the possibility that differences in core temperature may play a role in obesity and may represent a therapeutic area in future drug design,” added Osborn.
The scientists suspected that insulin in the brain might work to warm the body through a specific pathway involving signals that traveled from the brain’s preoptic area, down the spinal cord, to neurons that direct brown adipose tissue to expend energy to produce heat.
Brown adipose tissue, also known as brown fat, is distinct from white fat in that it burns calories rather than storing them. While in years past, brown fat was thought to exist in humans only when they are infants, recent studies have shown that brown fat deposits are also found in healthy adults, especially around their collarbones and necks. Interestingly, older people have less brown fat than younger people, and obese individuals have less than lean individuals.
Specifically, the scientists examined the effect of insulin injections in the preoptic area of rats on brown adipose tissue using computerized tomography (CT) scans and positron emission tomography (PET) scans. Rodents possess brown adipose tissue in two large masses on their backs between the shoulder blades.
When the activity of the brown fat was captured visually, the data confirmed the scientists’ projections.
Studies went forward examining the effects of insulin on metabolism, specifically by measuring the effect of insulin injections in the preoptic area of mice on oxygen consumption and carbon dioxide production. Again, results showed that metabolic rate increased with an increase in insulin.
All the techniques — PET/CT scan, metabolic studies, telemetric work — support the hyperthermic effect of insulin in rodent models.
The authors note that while their new paper illuminates a key piece of the puzzle of the body’s metabolic processes, it also raises many intriguing questions: how does insulin get to the brain’s preoptic area — does it cross the blood-brain barrier or is it produced locally? Are diabetics, who are insensitive to insulin in peripheral tissues, still sensitive to insulin in the brain; if so, could this dichotomy be used in the development of a new therapy? Could scientists find a way to use these new insights to increase energy expenditure for the purpose of weight loss?
The paper was published recently in an advance, online issue of the journal Diabetes, a journal of the American Diabetes Association, and will appear in the January print edition of the publication. Insulin causes hyperthermia by direct inhibition of warm sensitive neurons