Targeting Inflammation-Induced Obesity and Metabolic Diseases by Curcumin and Other Nutraceuticals

INTRODUCTION

According to Centers for Disease Control and Prevention (CDC), America is a home to the largest population of obese people in the world (http://www.cdc.gov/obesity/index.html). Thirty-three percent of adult Americans are obese, obesity has increased 60% within the past 20 years, 66% of American adults are overweight, one in six children are obese (http://www.cdc.gov/obesity/data/index.html), and obesity-related deaths have climbed to more than 300,000 a year, second only to tobacco-related deaths (191).The CDC indicated that American society has become obesogenic, characterized by environments that promote increased food intake, nonhealthful foods, and physical inactivity. According to the National Institute of Diabetes and Digestive and Kidney Diseases, approximately two-thirds of U.S. adults—nearly 167 million—are overweight, and nearly one-third (31.4%) are obese (http://www2.niddk.nih.gov/AboutNIDDK/OfficeofObesityResearch). In 2008, the nation spent $147 billion on obesity-related diseases. The list of morbidities associated with obesity is extensive. Obesity is a risk factor for heart disease, diabetes, stroke, and cancer. As many as 18 million Americans are currently diabetic, and the global incidence approaches 221 million cases. It is a leading cause of blindness, renal failure, and limb amputation for nontraumatic reasons. The total cost of this disease is approaching $130 billion per year in the United States alone (http://www.cdc.gov/obesity/index.html). Additionally, obesity may account for 14% of all cancer deaths in men and 20% in women (12). Some of the most common obesity-associated cancers include cancer of the colon, stomach, esophagus, gall bladder, ovary, breast, liver, endometrium, uterus, rectum, pancreas, cervix, and kidney, as well as non-Hodgkin’s lymphoma and multiple myeloma.

Obesity and metabolic syndrome are considered to be major public health crises not only in the United States but also globally. An expert panel convened by the National Institutes of Health has defined overweight as a body mass index (BMI) of 25 to 29.9 kg/m2 and obesity as a BMI of 30 kg/m2 or greater. According to the World Health Organization (WHO), as of 2005 there were approximately 1.6 billion overweight adults globally, of whom at least 300 million were clinically obese. The prevalence of overweight and obese American adults has steadily increased over the years in both genders, at all ages, in all racial and ethnic groups, at all educational levels, and for all smoking levels. Most studies show an increase in mortality rates associated with obesity. Individuals who are obese have a 10%-50% increased risk of death from all causes, compared with healthy-weight individuals. Most of the increased risk is due to cardiovascular causes. Obesity is associated with about 112,000 excess deaths per year in the U.S. population relative to healthy-weight individuals (http://www.cdc.gov/obesity/index.html).

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A condition related to obesity, metabolic syndrome is marked by a collection of unhealthy body measurements and abnormal laboratory test results that identify persons at high risk for developing cardiovascular disease and/or type 2 diabetes. Aggressive lifestyle modification and possible use of medications to treat the conditions that make up metabolic syndrome may reduce a person’s chances of developing heart disease or stroke. According to the CDC, an estimated 47 million Americans—nearly one-fourth of U.S. adults—have metabolic syndrome. These data illustrate the seriousness of the problem that most believe is preventable (22).

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Although caloric intake is one of the major contributors to obesity, people have known for centuries the role that diet plays in obesity. Certain kinds of diet (proinflammatory) can promote obesity, whereas other kinds (anti-inflammatory) can reduce it (3, 53, 93, 115, 142). A high-calorie, high-fat, and low-fiber diet usually promotes obesity; caloric restriction, exercise, and wholesome foods have been shown to reverse it (51, 151, 192). It is generally believed that highly processed, packaged, and refined foods loaded with sugar and hydrogenated oils are likely to promote obesity.

Knowledge of traditional medicine has allowed us to identify foods, food supplements, herbs, and spices believed to exhibit antiobesity effects. Some of these can be considered components of the complementary and alternative medicine (CAM) pharmacopoeia. According to findings released in July 2009 from the National Health Interview Survey (NHIS), Americans spent as much as $34 billion out of pocket on CAM in 2007. Whether CAM treatments are safe and effective, however, is unclear. The current review examines the role of inflammatory pathways in the pathogenesis of obesity and the modulation of obesity by various spice-derived nutraceuticals, with particular emphasis on curcumin.

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