Study: Extreme adiposity associated with obesity starts with inflammation in the brain

Obesity is a metabolic disease that is now considered to be an epidemic. In the United States, obesity is a major contributor to some of the leading causes of death among Americans, which include heart disease, diabetes and some types of cancer.

The main defining feature of obesity is the excessive accumulation and storage of body fat. Researchers have identified several contributing factors to this abnormal event, such as genetics and behavioral, metabolic and hormonal influences on body weight. But the culprit most commonly associated with obesity is the intake of too many calories coupled with a lack of exercise or physical activity. As pointed out by many studies, calories that are not burned through physical activities are stored by the body as fat.

Not surprisingly, the adult obesity rate in the U.S. is considerably high, exceeding 40 percent, because the standard American diet is made up of mostly sugar-laden beverages and fatty, highly processed foods. Aside from providing very little nutrients, research has found that these high-calorie foods make a person eat more than he actually needs because they are not satiating. This, combined with a sedentary lifestyle, is behind the alarming rise in both childhood and adult obesity rates seen in the country.

The link between inflammation and obesity

In an effort to understand what drives obesity at the molecular level, researchers at Ewha Womans University in South Korea decided to explore the mechanisms that lead to obesity. Their study, which appeared in the journal Nutrition Research, focused mainly on inflammation. Chronic inflammation has been linked to obesity and other serious conditions like heart disease and cancer.

According to an article published in Science, alterations in the gene sequence and increased expression of RIPK1, a key regulator of inflammation, are some of the main contributors to metabolic disease. When researchers inhibited the expression of RIPK1 in mice on a high-fat diet, they found that it not only reduced inflammatory responses, but also body weight and fat accumulation. This suggests that this inflammatory gene plays a crucial role in the development of obesity.

For their study, however, the Korean researchers focused on a mechanism that has only been proposed recently. This mechanism also involves inflammation, albeit in the brain instead of adipose tissue. Recent studies suggest that inflammation in the hypothalamus, the part of the brain that governs systemic metabolism, may also be a driving force behind obesity. (Related: Researchers conclude that drinking soda during pregnancy causes obesity in offspring.)

The researchers hypothesized that a high-fat diet could trigger metabolic inflammation via transcriptional changes (i.e., changes in gene expression) in the hypothalamus. To test their hypothesis, they characterized obesity-related in vivo transcriptional alterations in the hypothalamus and their effects on functional networks.

The researchers fed two groups of mice either a control diet or a high-fat diet for 20 weeks before conducting microarray and gene ontology analyses of the animals’ hypothalami. They reported that in the brains of mice on a high-fat diet, immune-related pathways such as inflammatory signaling were overly activated. This was not the case with mice on the control diet.

Meanwhile, in mice deficient in leptin — the hormone released by fat cells to tell the brain, particularly the hypothalamus, to suppress appetite — the researchers found that genes involved in inflammatory pathways and cancer pathways were highly expressed. They noted a similar overexpression in the hypothalami of mice on a high-fat diet, which confirms their hypothesis that brain inflammation is heavily involved in obesity.

Based on these findings, the researchers concluded that, rather than dietary fat and genetic mutation, inflammation in the hypothalamus is likely to be the cause of excessive fat accumulation associated with obesity.

Sources include:

Science.news

CDC.gov

ObesityMedicine.org

MayoClinic.org

TFAH.org

HSPH.Harvard.edu

Science.ScienceMag.org

ScienceDirect.com