Caffeine improves immune and metabolic function in diet-induced obese rats

This study was published by researchers at Taipei Veterans General Hospital (Taiwan) in the American Journal of Physiology Endocrinologoy and Metabolism



Obesity is associated with a variety of immune and metabolic problems, that are in large part related to the increased inflammatory state. Chronic inflammation in obesity results from immune cells, adipose tissue, muscle, and liver all having an “inflammatory profile.” Eventually, this can lead to development of insulin resistance and lower metabolic rates.

Caffeine has been shown to “downregulate” many markers of inflammation in animals and humans such as tumor necrosis factor-alpha (TNF), interleukin-6 (IL6), and monocyte  chemoattractant protein-1 (MCP-1). Additionally, caffeine is said to inhibit lopigenic genes (“fat making”) and improve blood lipids, lower fat mass, and increase insulin sensitivity. All of these would be highly beneficial to obesity-related metabolic abnormalities.

What did they study?

Researchers wanted to know if caffeine, in doses similar to what someone might consume in 2-3 cups of coffee per day, could perhaps modulate some of the inflammatory and metabolic dysfunction in an obese rat model. To do this, they investigated what happened on a molecular level after chronic caffeine treatment in tissues from the circulatory, immune, and metabolic systems.

How did they do it? 

To get the “fat rats”, researchers fed rats what is known in research as a “high fat diet”, or HFD. This diet contains ~34.9% fat (mostly saturated) by weight and had 60% of calories from fat. After 6 weeks on this diet, rats experienced fatty liver, obesity, and insulin resistance.

In addition to the obese rats, the researchers also had a “control” group of rats who were fed a normal chow diet (NCD).

Next, the HFD and NCD fed rats were assigned to one of two groups: either a 6 week caffeine treatment group (20 mg/kg/day of caffeine orally) or a control (vehicle) group who consumed no caffeine.

So, there were 4 groups in total. Obese rats who were both treated with caffeine and not treated, and a control group who was also treated with caffeine or not.

What did they measure? 

A LOT. (Major players discussed below)

In addition to measures of inflammation such as TNF, IL-6, and MCP (discussed above), researchers also did two measures which assess metabolic health: a glucose tolerance test (GTT) and an insulin tolerance test (ITT). What these allow us to see is how sensitive to insulin (higher is better, in most cases) a certain animal/human is. A glucose tolerance test similarly tests the body’s ability to “handle” a load of glucose. Both of these give an idea of the “metabolic health” of the rats.

Metabolic rate (whole body oxygen consumption over 24 hours), liver triglycerides, and muscle/adipose tissue biopsies were also performed to analyze.

What were the results? 

It is important to discuss, before each result, what changes happened in the high-fat diet fed mice. This allows us to get a sense of the deleterious effects the diet had, so we can then see how caffeine “therapy” may have had a beneficial effect.

Liver staining for presence of steatosis (NAS)

The high-fat diet increased levels of inflammatory markers and induced fatty liver in the diet induced obese mice. The HFD fed rats also had lower levels of anti-inflammatory markers, and a higher white blood cell count (signaling immune activation).

Notably,  Caffeine treatment for 6 weeks was able to suppress the inflammatory profiles of the HFD fed mice compared to those who received the “vehicle” (i.e. NO caffeine). Basically, caffeine “normalized” inflammatory markers like TNF AND IL-6 to levels seen in the normal chow fed rats.

Markers and bar graphs of protein levels of various inflammatory markers

The HFD + no caffeine group experienced significant insulin resistance. The HFD + caffeine group had greater insulin sensitivity parameters; they were essentially “protected” from developing insulin resistance on this diet.

Results of the glucose (left) and insulin (right) tolerance tests.

After HFD induced obesity, the rats had higher triglycerides, serum free-fatty acids, and indicators of fatty liver, as well as a decreased metabolic demand, increased fat mass, liver weight, and size/proportion of fat cells.

Chronic treatment with caffeine lowered the body weights of the HFD fed rats, and increased their metabolic rate. The changes in markers of fatty liver, levels of triglycerides, free fatty acids were all reversed in the caffeine-treated rats, suggesting protection from metabolic dysfunction.

Body weight
Body weight, lean mass/fat mass, adipose tissue weight, liver weight, and muscle/liver triglyceride content (TG)


Higher muscle, adipose, and liver inflammatory ICAM-1, TNF-alpha, IL-6, MCP-1 are associated with systemic/local inflammation in HFD rats – these were inhibited in caffeine treated HFD rats, suggesting caffeine is “anti-inflammatory” and can lower inflammatory mediators in cells.

Normalizing the circulating levels of the metabolic hormones adiponectin and the glucose transporter GLUT4 suggests that inflammation-associated insulin resistance was prevented in caffeine treated rats.

Oxygen utilization, C02 productoin, respiration, and energy expenditure



Caffeine treatment caused a change in “energy utilization” in the HFD rats – increasing metabolic rate and preventing the lowered metabolism resulting from the HFD. The formation of fat cells (de novo lipogenesis) was decreased in caffeine treated rats.

Caffeine, present in many beverages and consumed for centuries, may be a potential treatment, whereby it acts via multiple molecular mechanisms and pathways to inhibit obesity-related abnormalities. This is important in a time when diet-induced obesity/metabolic syndrome is a growing issue. Any therapy with a potential to even marginally inhibit deleterious effects of diet and environment should be explored.

If you enjoyed this post, check out my Medium page, where I talk more in depth about research studies, the research process, and generally wonder about issues in exercise, science, and nutrition today.

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Wei Liu et al. Effects and Mechanisms of caffeine to improve immunological and metabolic abnormalities in diet-induced obese rats. Am J Physiol Endocrinol Metab (2018). 314: E433-E447


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