Blood Glucose, Feeding Behavior, and Metabolic Fuels

Marshall McCue, Ph.D. shows how simultaneous collection of blood glucose, feeding behavior and metabolic fuel utilization compliment each other for studies of metabolic phenotyping.

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So, it’s possible to imagine that measurements of circulating metabolites and ingestive behavior and fuel oxidation would provide totally different insights into the biology of a mouse or a rat. But in this presentation, I’d like to show you how these three different types of measurements can actually provide complementary information and help inform studies of metabolic phenotyping.

This graph shows the minute-by-minute blood glucose levels of a single healthy mouse measured using a DSI Telemetry system. As you can see the values range from approximately 30 milligrams per deciliter to 120 milligrams per deciliter over a three-day period. Now if you squint at this graph, you can also see a circadian pattern whereby blood glucose levels are generally higher during the nighttime and lower during the daytime, but there’s quite a bit of variance in this data. So, is it possible for researchers to more deeply explore the behavioral and the physiological mechanisms that underlie this variance?

Fortunately, this mouse was housed inside a Promethion phenotyping cage which makes dozens of behavioral measurements every second. One of these measurements is feeding behavior. The blue bars on this graph show the timing and the magnitude of each individual feeding event and we can see that the mouse consumed meals as small as one milligram and as large as 90 milligrams over the three-day period. More interestingly, as indicated by the green arrows, we can see that the feeding events preceded the spikes in blood glucose by about 10 minutes. Now it’s not a coincidence that this is also how long it takes for ingested nutrients to become assimilated and enter the mouse’s circulation.

The Promethion phenotyping cages are also designed to continually measure the metabolic rate of the mouse in real time, and this allows researchers to calculate the animal’s energy expenditure as well as its respiratory exchange ratio or RER and this is shown in blue. The RER provides insights into the type of metabolic fuels that an animal is oxidizing in order to meet its metabolic demands. This graph illustrates the very high correlation between blood glucose levels and RER. It becomes clear that when blood glucose levels are at the lowest, the RER values drop to a value of near 0.7, suggesting that the mouse is predominantly oxidizing its lipid as its fuel source. Conversely when blood glucose levels are greater than 100 milligrams per deciliter, the RER of the mouse is above 0.9, suggesting that the mouse is predominantly oxidizing its carbohydrates as a fuel. Now interestingly even without any blood glucose measurements, it’s possible to quantify the mechanisms that are responsible for glucose homeostasis in your animal.

Let’s recap. The mouse is predominantly eating during the nighttime and this eating causes a shift toward oxidation of carbohydrates indicated by the increase in RER. We also see that feeding rates drop during the day, causing the mouse to increase its reliance on lipids as a metabolic fuel, indicated by a decrease in RER.

So, I hope that I’ve illustrated that, what might seem to be relatively unrelated measurements of blood glucose and feeding behavior and metabolic fuels, well they’re actually highly integrated components of the biology of a given model system. Now thanks to the Promethion system’s unique ability to synchronize multiple high-resolution data streams, each of which offer a different perspective into the physiology and the behavior of a living mouse, we can resolve complex physiological mechanisms that are central to the study of obesity, diabetes and other conditions.