Fighting Fat with Fat: New Potential for Obesity Pill
Fatty acid research reveals that a potential obesity pill may result from recent findings that show how good fat fights bad fat at the cellular level.
Fatty Acid Facts
The basic structure of a fatty acid is a chain of carbon atoms. Each carbon atom has four “bonds” that allows one carbon atom to connect to another carbon in a chain that can vary from two to several carbons in length. The remaining carbon bonds are bound to hydrogen atoms with the exception of the first carbon atom that has a carboxyl (COOH) group attached at one end. The carboxyl group is what gives the fatty acid its “acid” label.
The simplest fatty acid is the acetic acid found in vinegar. It consists of a single carbon atom attached to one carboxyl group and three hydrogen atoms. All fatty acids begin their structure like acetic acid, but have longer chains of carbon atoms following the carboxyl-bonded carbon atom.
When fatty acids are grouped together they form into fat. For example, three chains of fatty acids attached to each other form the familiar triglyceride fat we hear about when we have our blood work done during a physical.
Two types of fatty acids play an important role in our health: saturated and unsaturated fatty acids. Saturated fatty acids share only a single bond between each carbon atom in the chain with the remaining carbon bonds “saturated” with hydrogen atoms. Unsaturated fatty acids share two bonds at least once (mono-unsaturated) or more (poly-unsaturated) between some of the carbons in the fatty acid chain.
Palmitic acid is an example of a fatty acid that is saturated. When chains of this fatty acid are grouped together we get a saturated triglyceride fat. This saturated fat is solid at room temp. Butter made from milk, which is chiefly saturated animal fat is an example of solidified fat.
In contrast, oleic acid has one double bond between carbon atoms in its chain and is therefore a mono-unsaturated fatty acid. Linoleic acid has multiple carbon-to-carbon double bonds and is called a poly-unsaturated fat. Fats consisting of oleic and linoleic fatty acid molecules are liquid at room temp and are called oils. Corn oil is one example of an oil that contains a large amount of poly-unsaturated linoleic fatty acids.
A diet rich in fat is a major risk factor for heart disease, diabetes and obesity. However, not all fats are bad for us. Saturated fats like the type we get from butter and lard are bad for our health, whereas the mono-unsaturated and poly-unsaturated fats we can find in plants and fish are considered to be beneficial toward fighting heart disease, diabetes and obesity.
Previously, researchers did not know how our cells are able to tell one fat type from another and thereby elicit a response that leads to a beneficial or adverse cellular event. However, in a recent paper published in the September 30 issue of the journal Cell, researchers at the University of California San Diego School of Medicine believe that they have determined how cells recognize and discriminate between saturated and unsaturated fatty acids.
Earlier studies had shown that saturated fatty acids, such as palmitic acid, activate “Jun kinases” (JNK), which are key regulatory proteins believed to cause the development of type 2 diabetes, insulin resistance, obesity and atherosclerosis. Kinases are proteins that modify other proteins and small molecules such as fats, to act as a signal toward a subsequent step in a biochemical or molecular process. An unsaturated fatty acid, however, such as palmitoleic acid (POA) does not activate Jun kinases; but rather, can block Jun kinase activation initiated by palmitic acid.
The researchers had observed that both types of the fatty acids behave differently within the cell membrane. The only difference between the saturated fatty acid palmitic acid and the unsaturated fatty acid palmitoleic acid is a single double bond in the carbon chain of the unsaturated palmitoleic acid. Their biochemical difference and the difference in cell membrane behavior led the researchers to hypothesize that proteins within the cell membrane that were affected differently by different types of fatty acids were what allowed the cell to discriminate between saturated and unsaturated fatty acid types.
Using cultured cells and animal models, the researchers began looking for kinases that are part of the cell membrane that are specific for saturated fatty acid activation. What the researchers found was a cell membrane protein kinase they identified as c-Src that activates JNK when the cell is treated with palmitic or other saturated fatty acids. The c-Src kinases are “pushed” by the saturated fatty acids into accumulated regions that are conducive toward JNK activation. Conversely, they also found that when the cells were treated with the unsaturated fatty acid palmitoleic acid, that the unsaturated fatty acid changes the c-Src distribution within the cell membrane and thereby prevents JNK activation.
The results of the study lead the researchers to theorize that their findings could lead to an anti-obesity supplement that acts at the molecular level in cells.
“These findings not only explain the long-standing enigma regarding the differential health effects of saturated and unsaturated fatty acids,” said senior author Michael Karin, PhD, Distinguished Professor of Pharmacology in UC San Diego’s Laboratory of Gene Regulation and Signal Transduction, “they also provide improved tools and a mechanistic framework for the potential development of dietary supplements to treat obesity, estimated to be worth billions of dollars per year.”