The Obesity Epidemic

For over a decade, obesity has been called an “epidemic”, both in the popular and scientific literature. Traditionally, the term “epidemic” is associated with a highly contagious disease that carries with it a significant risk of mortality. A comprehensive review of observational studies (1) suggested that obesity did not fit this definition, despite the use of the term in a widely disseminated report by the World Health Organization in 2002.

Regardless of the etymological fine points, the worldwide prevalence of obesity and its associated health risks are clear. These risks include type 2 diabetes, hypertension, several cancers, gall bladder disease, coronary artery disease and stroke (2). Yet, the debate over obesity and options for reducing its risks has become increasingly polarized. As a result, some health researchers are advocating a “health at every size” (HAES) approach to address the social, cultural and lifestyle implications of obesity (2).

White, Brown or Beige?

The primary physiological manifestation of obesity is an accumulation of adipose (fatty) tissue. Although the traditional role of adipose tissue is energy storage, it is now being viewed as an endocrine organ and a critical component of the immune system (3). A common consequence of obesity, insulin resistance, occurs as a result of adipose tissue inflammation, and adipocytes secrete a variety of proteins that regulate energy metabolism (3). Buildup of adipose tissue, especially in the abdomen, is a key part of the cluster of conditions known as metabolic syndrome.

Given the serious health consequences of obesity, is there such a thing as “healthy” (or at least benign) obesity? There are two primary types of adipocytes: white and brown. White adipocytes store energy, while brown adipocytes regulate energy metabolism and help maintain body temperature; their abundance decreases as humans age. Further, white adipocytes can be converted to brown adipocytes by so-called beiging (see this blog post). In obese individuals, inflammation is associated with a reduction in beiging and a consequent reduction in insulin sensitivity (3). Therefore, increasing the rate of beiging in obese individuals or activating existing brown adipose tissue could, in theory, have beneficial health effects.

More Coffee, Please

A recent study examined the effects on brown adipose tissue of a substance familiar to most humans—caffeine (4). Activation of brown adipocytes involves a mitochondrial membrane protein known as uncoupling protein 1 (UCP1), which increases heat generation and the metabolism of nutrients such as glucose and lipids. Both brown and beige adipocytes respond to a variety of nutrients, but the direct effect of caffeine on brown adipocytes is unknown. Since caffeine has been associated with weight loss and increased energy expenditure, the researchers decided to examine its effects on mouse mesenchymal stem cells induced to differentiate into adipocytes in vitro, as well as in a small, follow-up study in humans.

The in vitro results demonstrated that caffeine increased the expression of UCP1, as well as the rates of glycolysis and oxidative phosphorylation. Further, caffeine increased the expression of beiging and brown-selective genes. Bioimaging of a small group of healthy human volunteers showed increased heat production in brown adipose tissue after drinking coffee, compared to water. The authors conclude that further studies are needed to examine “whether comparable effects are seen in fully differentiated adipocytes and primary cells, as well as in diabetic and/or obese individuals.”

The Power of Polyphenols

Another recent publication took a different approach to defining healthy obesity. Aires et al. (5) noted that obesity is not always associated with metabolic disorders; conversely, metabolic abnormalities occur even in lean individuals. They stated that “a paucity of experimental data unambiguously support a direct and causal relationship between adipose tissue dysfunction, metabolic disorders and life expectancy.”

Accordingly, the study was designed to answer two questions:

1. What is the impact of obesity on adipose tissue composition and longevity, when induced by a high-fat/high-sucrose (HF/HS) diet?
2. Are metabolic dysfunction and abnormalities in adipose tissue composition preventable?

The researchers compared mice (8-10 weeks old) randomly assigned to one of three diet groups: standard diet, HF/HS diet or HF/HS diet supplemented with polyphenol-rich plant extract (PRPE). As early as 2 weeks, the HF/HS diet was associated with a more rapid weight gain than the standard diet, and the HF/HS-fed mice had a significantly shortened lifespan. The HF/HS-fed mice had significantly higher plasma glucose and cholesterol levels, increased oxidative stress and greater lipid intolerance than standard-fed mice.

Despite the presence of similar obese traits between HF/HS-fed and HF/HS/PRPE-fed mice, the latter group had a markedly increased lifespan (mean 689 days vs. 381 days), lower cholesterol levels and lower endotoxin levels. Adipose tissue analysis demonstrated that PRPE did not affect adipocyte tissue hypertrophy or adipocyte size, but it markedly reduced the number of infiltrating macrophages. Further, RNA-Seq analysis of adipose tissue confirmed that PRPE downregulated several immune inflammatory processes.

The authors conclude that their study “is the first to consistently report that supplementation of the HF/HS diet with PRPE significantly reduced the circulating level of the [malondialdehyde] lipid peroxidation marker, substantially reduced the levels of mobilizable cholesterol and cholesterol oxides in the adipose tissue, and substantially increased median lifespan.”

The results from these studies will need further analysis to support their conclusions. What’s clear is that there are no simple solutions to address the complex issues surrounding obesity. However, a promising conclusion of both studies is that dietary intervention can have beneficial results, independent of weight loss.

Now, if you’ll excuse me, I’m going to have another cup of coffee—or perhaps a glass of red wine.

1. Shepard, R.J. Obesity in 2018. Do we have an epidemic, and if so what caused it? (2018) Health Fit. J. Canada 11:53.
2. Penney, T.L. and Kirk, F.L. (2015) The Health at Every Size paradigm and obesity: missing empirical evidence may help push the reframing obesity debate forward. (2015) Am. J. Public Health 105:e38.
3. Stolarczyk, E. Adipose tissue inflammation in obesity: a metabolic or immune response? (2017) Curr. Opin. Pharmacol. 37:35.
4. Velickovic, K. et al. (2019) Caffeine exposure induces browning features in adipose tissue in vitro and in vivo. Sci. Rep. 9:9104.
5. Aires, V. et al. (2019) Healthy adiposity and extended lifespan in obese mice fed a diet supplemented with a polyphenol-rich plant extract. Sci. Rep. 9:9134.

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Ken Doyle

Ken is a science writer at Promega Corporation. Although his PhD is in molecular biology, he enjoys researching and writing about everything from M-theory to graptolites. When he's not spending time with family or serving his canine and feline overlords, Ken engages in a quest for a mythical creature known as "spare time". If he succeeds, he hopes to return to writing fiction so he can keep his brain in balance.

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