A new candidate pathway for treating visceral obesity

Brown seems to be the color of choice when it comes to the types of fat cells in our bodies. Brown fat expends energy, while its counterpart, white fat stores it. The danger in white fat cells, along with the increased risk for diabetes and heart disease it poses, seems especially linked to visceral fat. Visceral fat is the build-up of fat around the organs in the belly.

So in the battle against obesity, brown fat appears to be our friend and white fat our foe.

Now a team of researchers led by Jorge Plutzky, MD, director of The Vascular Disease Prevention Program at Brigham and Women's Hospital (BWH) and Harvard Medical School has discovered a way to turn foe to friend.

By manipulating the metabolic pathways in the body responsible for converting vitamin A-or retinol -into retinoic acid, Plutzky and his colleagues have essentially made white fat take on characteristics of brown fat. Their findings put medical science a step closer in the race to develop novel anti-obesity therapies.

The study will be published online on May 6, 2012 in Nature Medicine.

Retinoids, which are molecules derived from vitamin A metabolism, are responsible for many biological functions. One such function is the control of fat cell development and actions. A key step in retinoid metabolism occurs with help from an enzyme called retinaldehyde dehydrogenase 1, or Aldh1a1. The researchers saw that in humans and mice, Aldh1a1 is abundant in white fat cells, especially in the more dangerous visceral fat (sometimes referred to as abdominal fat or belly fat).

Visceral fat surrounds the organs and is connected with various diseases such as diabetes, hypertension, elevated triglycerides and the fast growing phenomenon known as metabolic syndrome.

Unlike stomach fat that is located under the skin, visceral fat proceeds as a lively endocrine organ releasing hormones that can lead to diabetes and insulin resistance.

To be diagnosed with intra-abdominal adiposity, your waist must be larger than 40 inches in men and 35 inches in women. The common apple-shaped body is greatly associated with elevated levels of visceral fat storage. Unlike subcutaneous fat which jiggles on the outside, visceral fat environs the organs and can’t be visually seen.

When Aldh1a1 was inhibited in white fat cells, those cells began acting like brown fat cells. One of the defining characteristics of brown fat is its ability to release energy as heat. Mice with either deficiency or inhibition of Aldh1a1 become protected against exposure to cold. The researchers saw this classic indicator of brown fat and its ability to generate heat by oxidizing fat (a chemical reaction involving oxygen) in their research.

Especially exciting for the prospects of targeting Aldh1a1 for therapeutic benefit, the researchers found that knocking down expression of the Aldh1a1 gene by injecting antisense molecules into mice made fat by diet resulted in less visceral fat, less weight gain, lower glucose levels, and protection against cold exposure as compared to control mice.