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Research Newsletter-Spring/Summer 2008


Donald B. Jump, Ph.D.
Professor of Nutrition and Exercise Sciences
LPI Principal Investigator

We are inundated with information on diet. The balance between dietary carbohydrate, fat, and protein is a hot topic for the media. The goal of this article is to explain some basic features about dietary fat, why we need fat in our diet, and when we get into trouble with dietary fat.

Why we need fat in our diet

Dietary fat plays several key roles in our physiology and well-being. It provides flavor to food. Ingestion of fat is important for the intestinal absorption of lipid-soluble vitamins like vitamins A, D, E, and K. Fat is a key source of metabolic energy. Components of fat are also important building blocks of all cells in the body. Fat, in the form of glycero- and sphingolipids, makes up the bulk of cellular membranes. These complex lipids are composed of fatty acids bound to glycerophosphate or sphingosine. Cellular membranes serve as barriers between compartments, such as the inside and outside of the cells, and are important for the maintenance of cellular structural integrity. They also play important roles in metabolism and in the regulation of cell function. Fatty acids also function as signaling molecules, thereby regulating cell function.

Types of fat

There are four kinds of fat: saturated, trans, monounsaturated, and polyunsaturated fat. These terms refer to the structure of the fatty acids found in fat. Saturated fatty acids have no double bonds between carbon atoms and are rigid molecules (see Figure). Monounsaturated fatty acids have a single double bond, while polyunsaturated fatty acids have two or more double bonds. Trans fats, also known as partially hydrogenated fats, are formed through the industrial processing of liquid vegetable oils. Trans fats are unsaturated fatty acids with the double bond in the trans configuration. Most naturally occurring double bonds in fatty acids are in the cis configuration. The double bond configuration affects the flexibility of the molecule around the double bond. As such, trans fatty acids are rigid like saturated fats.

Structures of common dietary fatty acids

Unsaturated fatty acids are also grouped into classes, depending on the position of the first double bond relative to the methyl (-CH3) end of the molecule (see Figure). Omega-3, omega-6, and omega-9 are common dietary mono- and polyunsaturated fatty acids. The flexibility of these molecules increases with the number of double bonds.

Fatty acids in foods are incorporated into several types of complex lipids like triglycerides, cholesterol esters, and phospholipids. The fatty acid composition of foods is complex. For example, pork fat consists of 40% saturated fatty acids (SFA), 45% monounsaturated fatty acids (MUFA), and 15% polyunsaturated fatty acids (PUFA), while olive oil is 14% SFA, 74% MUFA, and 12% PUFA.

For us to utilize fat in food, complex lipids must first be hydrolyzed in the small intestine. The released fatty acids are absorbed by intestinal cells where they are converted to triglycerides for packaging into lipoprotein particles called chylomicrons, which circulate in the blood. Chylomicrons are vehicles for the delivery of fat to cells. Enzymes like lipoprotein lipase on the surface of cells degrade chylomicron lipids so that fatty acids can enter cells. Once in cells, fatty acids are processed through various metabolic pathways, such as assembly into triglycerides for storage, assimilation into phospholipids for membrane synthesis, or oxidation in the mitochondria for energy production.

Although we get much of our fat requirement from the diet, we have the capacity to synthesize fat in adipose tissue and in the liver. Excess carbohydrate consumption, for example, results in the conversion of carbohydrate (glucose) to palmitic and oleic acid (see Figure); these fatty acids are assimilated into triglycerides for storage. Some fatty acids, however, cannot be synthesized in our bodies. These "essential fatty acids," linoleic acid (omega-6) and alpha-linolenic acid (omega-3), are found in vegetable oils like corn and canola. Walnuts are also a good source of alpha-linolenic acid. Essential fatty acids are precursors to the very long chain fatty acids, arachidonic acid (ARA, omega-6) and docosahexaenoic acid (DHA, omega-3) (see Figure). ARA and DHA function as both structural and regulatory molecules. Deficiency of essential fatty acids leads to multiple pathologies associated with reproductive failure, poor visual acuity, learning disabilities, capillary fragility, skin lesions, fatty liver, and other problems. Therefore, the food industry supplements certain foods with PUFA to prevent these problems. For example, Enfamil LIPIL® from Mead Johnson Nutritionals is a popular infant formula supplemented with both ARA and DHA.

Fatty acids are signaling molecules

In addition to serving as sources of metabolic energy and structural elements of cells, fatty acids are now recognized as signaling molecules. In many cases, fatty acids act like hormones to control cell function. ARA, for example, is a precursor for eicosanoids like prostaglandins. Prostaglandins are oxidized lipids that bind receptors on cells. Activation of prostaglandin receptors initiates signaling cascades that control many physiological functions. Eicosanoids derived from omega-6 PUFA are typically pro-inflammatory. Omega-3 PUFA like DHA and eicosapentaenoic acid (EPA), which are found in fish, interfere with the conversion of omega-6 PUFA to eicosanoids, thereby exerting antiinflammatory functions. Moreover, when EPA and DHA are oxidized to eicosanoids and docosanoids (resolvins), they form lipids with anti-inflammatory properties.

Fatty acids also regulate gene expression, controlling the types of proteins cells make. Changes in gene expression affect metabolism, inflammation, and cell growth and division. Fatty acids bind to and activate peroxisome proliferator activated receptors, which control the expression of multiple genes affecting whole body fatty acid oxidation, storage, and inflammation. PUFA also target other proteins in cell nuclei that regulate gene expression, including nuclear factor κB (NFκB), sterol regulatory element binding protein- 1 (SREBP1), carbohydrate regulatory element binding protein (ChREBP), and Max-like factor-X (MLX). NFκB controls the production of proteins involved in inflammation and immunity. ChREBP, MLX, and SREBP1 control the production of proteins regulating whole body glucose metabolism and fatty acid synthesis and storage.

Finally, cellular membranes contain microdomains called "lipid rafts." Lipid rafts harbor key proteins involved in transferring signals from outside to inside cells. Changes in the structure of lipid rafts by the composition of lipids in membranes alter cell signaling and function. Fatty acids are important regulatory molecules that use diverse routes to control multiple facets of cell metabolism, division, and differentiation, as well as inflammation.

What is wrong with fat?

The type and quantity of fat ingested affects our health. Health problems arise when we ingest too much fat or the wrong type of fat. For example, increasing saturated and trans fat in the diet is associated with elevated blood LDL cholesterol, a pro-atherogenic risk factor. The American Heart Association recommends consuming less than 7% of calories as saturated fat and less than 1% as trans fat. Many experts recommend eliminating trans fat altogether. In contrast, increasing omega-3 PUFA in the diet is anti-atherogenic, it protects against heart disease. Helpful information on the fat composition of foods can be found at

Fat is typically stored in the body's adipose tissue as triglyceride and cholesterol esters. High fat diets lead to the accumulation of fat in non-adipose tissues like liver, heart, muscle, and pancreas. The accumulation of excess fat in the heart promotes a form of cardiomyopathy, and too much fat in the liver can progress to steatohepatitis (inflamed liver), fibrosis, and cirrhosis. Accumulated fat in tissues promotes lipotoxicity, a syndrome characterized by caspase activation and programmed cell death (apoptosis) brought on by the accumulation of lipid-derived signaling molecules (diacylglycerol, ceramide, and reactive oxygen species). Too much ingested fat also interferes with the function of insulin. Insulin normally promotes glucose uptake by tissues for oxidation and storage, but impaired insulin action affects both glucose and lipid metabolism, leading to hyperglycemia and hyperlipidemia, which are risk factors associated with non-insulin dependent diabetes mellitus (NIDDM). NIDDM is the most common form of diabetes in Western societies. Complications arising from diabetes include blindness (retinopathy), heart disease, nerve damage (neuropathy), and kidney damage (nephropathy). More information on diet and diabetes can be found at the American Diabetes Association Web site.

Just as too much dietary fat is harmful, eating the wrong type of fat is also harmful. Western diets contain too much saturated and omega-6 PUFA and too little omega-3 PUFA. The balance between omega-6 and omega-3 PUFA is important in the context of the production of pro- versus anti-inflammatory lipids. Chronic diseases like atherosclerosis and diabetic retinopathy are inflammatory diseases of the vasculature. Omega-6 PUFA are pro-inflammatory, while omega-3 PUFA—particularly EPA and DHA—are anti-inflammatory. Therefore, the balance between omega-3 and omega-6 lipids is an important determinant in the progression of chronic inflammatory diseases. Unfortunately, humans do not efficiently convert the common plant-derived omega-3 PUFA, alpha-linolenic acid, to EPA and DHA. The American Heart Association recommends increasing omega-3 PUFA intake by consuming fish like salmon and tuna, which are good sources of EPA and DHA.

As we know, the diet is a key environmental factor affecting our health. It is also one factor that we can control. As such, a balance of fat—the amount and type—is important to promote health and prevent disease. Additional information on the role of dietary fat and health can be found on the Linus Pauling Institute Micronutrient Information Center.

Last updated June 2008