Metabolic diseases cause the greatest morbidity and mortality worldwide. Dramatic rises in obesity and related disorders have occurred globally in just decades, sparing no age groups. Excessive caloric intake, an inactive lifestyle and genetic factors are driving the current health crisis. The human body primarily stores this excess energy or calories in the form of fat.

There are 2.3 billion overweight adults in the world of which 700 million are obese (World Health Organization 2015). Thus, 40% of adult men and women in the world are either overweight or obese. In the U.S., about 20% of the healthcare budget targets obesity and its related disorders. No public policy or widespread therapeutic strategy has proven effective despite massive effort and funding worldwide.


Physiologic stress due to excess fat and its by-products leads to altered metabolism and obesity-related disorders: (click on each tab to learn more about each disorder/disease)

This common condition is caused by excessive fat in liver cells, which in Medicine is called steatosis. It is a manifestation of disordered fat and energy metabolism that extends beyond the liver. People with fatty liver disease can trigger activation of the immune system which in the liver causes “steatohepatitis” an aggressive inflammation that causes scarring (fibrosis) and can lead to cirrhosis and liver cancer. Occasionally, people with fatty liver disease develop liver cancer even when they do not have cirrhosis. One-quarter of adults worldwide and one-third of adults in the U.S. have fatty liver. It is the most common liver disease in North America and one of the leading causes of cirrhosis and liver cancer.

Increased body mass index correlates with increases in circulating levels of systemic inflammatory molecules including C reactive protein (CRP). During the past decade, accumulating evidence strongly links the amount and distribution of adipose tissue (AT) with inflammation in other tissues. The pro-inflammatory effect of fat began to unravel just over 20 years ago when it was noted that TNF-alpha expression was increased in AT of obese mice. Adipose tissue contains not only adipocytes (the cells that store fats) but also other cells including macrophages that secrete cytokines and are integrally involved in immune function and inflammation.

When caloric intake exceeds physiological need, the amount of AT increases and the non-adipocyte cell composition changes, resulting in marked increases in the number of AT macrophages and release of inflammatory cytokines, locally and into the circulation. Accumulating evidence suggests that lipids, the adipocytes and non-adipocyte cells in different types of AT interact, including with other tissues, in setting the systemic inflammatory state. For example, the systemic inflammatory marker, CRP, is produced in the liver, driven by interleukin 6 (IL-6), a cytokine released from AT. Notably, the visceral AT, which surrounds the intestines, secretes more pro-inflammatory cytokines (including IL-6) per gram of tissue than subcutaneous AT. The result and clinical manifestations of obesity-associated systemic inflammation varies in different tissues.

Cardiovascular disease is the leading cause of death in many countries, correlating with national obesity rates. Atheroma, the pathological change that occurs in artery walls and causes heart attacks, strokes and other diseases, is caused by local accumulation of fats in conjunction with fat-associated inflammation. While elevated blood levels of bad forms of cholesterol predispose to fatty arteries, it is now clear that local and systemic inflammation also play key roles in atheromatous plaque formation and rupture.

Obesity increases the circulating levels of inflammatory mediators, and lowers the levels of anti-inflammatory mediators. The vascular protective effects of drug regimens such as statins, which reduce inflammation as well as bad cholesterol, emphasize the importance of inflammation in heart attacks and strokes. FGH’s novel molecules, coined “Fatostatins” by Dr. Salih Wakil in 2009, lower cholesterol and other forms of atherogenic fat, including triglycerides, and also reduce adipose tissue stores, including visceral fat, thus dampening inflammation more systemically.

Obesity increases risk for type II diabetes by inducing insulin resistance. Although insulin resistance likely culminates from more than one mechanism, the excess adipose tissue itself is the key factor; insulin sensitivity improves when negative energy balance is achieved in response to exercise, calorie restriction and reduction in adipose tissue (weight loss). Pharmacologically controlled inhibition of lipogenic SREBP activity is therefore anticipated to significantly improve insulin sensitivity, improve glycemic control and improve the “lipotoxic” profile of hyperlipidemia and systemic immune activation associated with diabetic complications.

There is strong association between obesity and many types of cancers. These cancers include: colon, esophageal, gastric, pancreas, liver, gallbladder, kidney, post-menopausal breast, ovarian, uterine, prostate and some blood cancers. Unsurprisingly, this list, like the obesity epidemic, is expanding. The unifying feature of cancers is unregulated cell growth and proliferation. In some tissues this can result from chronic inflammation. Molecular pathways that link obesity and certain cancers are still being unraveled and include intracellular signaling pathways such as the PI3K/Akt/mTOR cascade, which regulates cell proliferation and survival. It is logical to conclude that therapeutic regulation of fat metabolism and obesity should reduce cancer incidence and could prove a useful therapeutic adjunct in treating some forms of cancer.

Learn more about our Technology