Can Caffeine Help Tackle Obesity via Brown Fat Activation?

Liam Davenport

June 26, 2019

Drinking coffee appears to cause activation of brown adipose tissue (BAT), say UK researchers in findings they contend could point to novel ways of tackling obesity and diabetes.

Michael E. Symonds, PhD, of University of Nottingham, United Kingdom, and colleagues initially conducted a series of experiments in stem cell-derived fat cells (adipocytes) and found that caffeine exposure increased mitochondrial activity and proliferation, as well as gene expression linked to 'browning' of fat cells.

Next, in a small number of healthy volunteers, they used thermal imaging to measure temperature changes in the neck (supraclavicular region) — where the greatest abundance of BAT is found — in response to drinking coffee or water.

The results, published by Scientific Reports on June 24, show that coffee drinking was followed by significant increases in temperature in the supraclavicular region relative to the body surface temperature.

"This is the first study in humans to show that something like a cup of coffee can have a direct effect on our brown fat functions," Symonds said in a press release issued by his institution.

"The potential implications of our results are pretty big, as obesity is a major health concern for society, and we also have a growing diabetes epidemic, and brown fat could potentially be part of the solution.

"We now need to ascertain that caffeine as one of the ingredients in the coffee is acting as the stimulus or if there's another component helping with the activation of brown fat. We are currently looking at caffeine supplements to test whether the effect is similar."

But obesity expert Caroline M. Apovian, MD, of the Department of Diabetes & Endocrinology, Boston University School of Medicine in Massachusetts, who was not involved in the study, takes issue with many of the conclusions that the authors draw, describing them as a "jump."

Among other issues, thermal imaging is not a proven method for measuring changes in BAT activity, she maintains.

First Study to Show That Caffeine Effects in Vitro Translate in Vivo

Adaptive thermogenesis, which is the production of heat in response to environmental or dietary factors, occurs in the mitochondria of brown adipose tissue. The latter is functionally distinct from white adipose tissue, which predominates in obesity and is primarily concerned with energy storage.

Until relatively recently, it was thought that brown fat in humans existed only in babies; 10 years ago, three papers published in the NEJM reported that some adults had small pockets of brown fat — which is brown because of the mitochondrial content — in supraclavicular and abdominal areas.

However, the amount of BAT decreases with age and is negatively correlated with body mass index (BMI) — so people in their 60s, 70s, and 80s and very obese people have little or no brown fat.

For this work, Symonds and colleagues set out to examine the effect of caffeine on BAT thermogenesis in vitro and in vivo.

First, in human stem cell-derived adipocytes exposed to caffeine at a concentration of 1 mM — chosen after research to determine the optimum concentration for viability and differentiation of such cells — the investigators showed increased UCP1 protein abundance and cell metabolism with enhanced oxygen consumption and proton leak.

These functional responses were associated with browning-like structural changes in mitochondrial and lipid droplet content, and caffeine also increased markers of mitochondrial and lipid metabolism.

In the in vivo setting, the researchers studied nine healthy volunteers (mean age 27 years; normal BMI [mean BMI 23 kg/m2) who had not engaged in vigorous exercise or consumed caffeine, drugs, or alcohol for at least 9 hours, and who had not eaten for at least 2 hours.

The volunteers underwent thermal imaging of the supraclavicular region before and after consumption of either instant coffee or water alone, both heated to 71°F (22°C).

The team chose this method of assessing the thermogenic effect of coffee on supraclavicular BAT as it is "well correlated" with the gold standard technique of radiolabeled glucose uptake into BAT on positron emission tomography-computed tomography (PET-CT) during cold exposure, they explain.

The authors maintain that, as PET-CT assessment has to be undertaken in fasted individuals due to the confounding effect of glucose uptake by the muscles, thermal imaging is a "practical method" for detecting changes in BAT activity in response to ingestion.

The results showed that drinking coffee led to a significant increase in temperature in the supraclavicular region corresponding to BAT stores both in comparison with baseline (P < .001) and body surface temperature (P < .01). No significant temperature changes were recorded following water consumption.

"This is the first study to determine that the stimulatory effects of caffeine on UCP1 seen in vitro can be translated to adult humans ingesting caffeine in a commonly consumed coffee beverage," the researchers say.

"The increase in temperature of the region which co-locates with BAT observed with caffeine ingestion is indicative of an increase in BAT activity following a relatively low dose of caffeine from a single standard cup of coffee."

"Future intervention studies can now be undertaken to assess whether caffeine-induced BAT activation in humans is dose-dependent, [to] refine the minimal intake required for a BAT response, and explore whether comparable effects are seen in fully differentiated adipocytes and primary cells, as well as in diabetic and/or obese individuals," they conclude.

But Moving in Vivo Is Complicated; Did They Do the Right Test?

Apovian told Medscape Medical News that, while the study is "intriguing," one problem is that it combines coffee and caffeine consumption, rather than separating them out.

"That's a jump, because there are studies in the literature showing that the combination of caffeine with other things can promote weight loss," she said, stressing that neither caffeine alone, nor coffee, have been shown to have this effect.

She continued: "What we see with coffee drinkers is that there seems to be an improvement in mortality. They live longer, but we just don't know why that is. It doesn't seem to be the caffeine, so the question is: Is it just because coffee drinkers also do other healthy things, like exercise and eat well?"

Another issue with the study, Apovian said, is that although it shows that caffeine promotes BAT function, this has also been demonstrated with cold exposure.

"If that's all you need to do to lose weight, then we could all just go into a cold climate or into a refrigerator and lose weight, but that's not the way it works," she said.

And while Apovian nevertheless thinks that the in vitro studios were well conducted, she takes the greatest issue with the use of thermal imaging as a surrogate for PET-CT.

It is "not a good measure of activation of BAT in that area" and there are "a lot of problems with that method," she asserted.

When researchers move from in vitro studies to humans they "have to be very careful that they're doing the right test," she cautioned.

She believes that the results therefore need to be validated in a follow-up PET-CT study of the supraclavicular BAT and, if it "lights up more," then the coffee might be responsible for the increased activity.

"So that part [of the study] I don't buy, but the rest of it is pretty good," she summarized.

The study was funded by the EU-CASCADE fellowship scheme from the European Union's 7th FP PCOFUND-GA-2012-600181, CONACyT, Mexico with support from The Cardiometabolic Disease Research Foundation (Los Angeles, California). The study was supported by the Biotechnology and Biological Sciences Research Council. The Zeiss Elyra PS.1 microscope, the processing computers, and the software were funded by BBSRC BB/ L013827/1 (Multidisciplinary Super Resolution Microscopy Facility).

The study authors and Apovian have disclosed no relevant financial relationships.

Scientific Reports. Published online June 24, 2019. Full text

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