Preventing Obesity and
Obesity-Related Diseases

by Morten Bryhn, MD, Ph D

5/7/2002

High fat diets lead to excess weight gain but some, especially polyunsaturated fatty acids have other functions including interacting with cellular proteins, which turn genes off and on. These are known to encode proteins controlling energy production. Ingestion of omega-3 fatty acids in particular is associated with reduced adiposity.

More and more individuals are becoming overweight and obese, a condition now considered to be the most common nutritional disorder in the industrialised world today. Overweight and obesity can be defined by a body-mass index exceeding either 25% or 30%, respectively. Body-mass index is calculated by dividing weight in kg by the square of the height in meters. Normal values range from 18 to 25%. In the US 34% of the population is overweight and another 27% is obese. This means that more than 60% of the entire population has what can be defined as a weight problem, which is likely to cause severe health problems, particularly diabetes, hypertension, and elevated blood lipids, all risk factors for cardiovascular disease.

Overweight and obesity is caused by an imbalance between energy intake and energy use. In the industrialised world we tend to eat too much and exercise too little. However, the likelihood of getting fat under these conditions is not the same for everyone, as witnessed by the fact that slim individuals exist under the same conditions as those who become overweight. A sound strategy for prevention of weight gain or losing weight should take into account measures of energy expenditure and dietary advice based on the individual. This is by no means new. What is new, however, is the understanding of how nutritional factors can impact on bodyweight. This is particularly true for dietary fats. Recent advances in the study of white adipose tissue and dietary fats has shown a complex interplay between hormones involved in lipid metabolism and fatty acid gene interactions. The revelation that nutritional factors can control gene expression has opened up the possibility of developing novel therapeutic alternatives to treat obesity in the future. However, the basic mechanisms of why we are, as a population, increasing our bodyweight will always be important.

Fat is the most calorie dense nutrient and high fat diets are linked to excess weight gain, but not all fats are equal. Changing the fat composition of your diet can even help lose weight. Fats are composed of fatty acids. In the gastrointestinal tract fats are broken down into fatty acids by lipases and absorbed into the intestinal cells. In intestinal cells, the lymphatic system and the liver, fatty complexes are produced to transport fatty acids. In the circulation these fatty acids are released by lipases entering into cells membranes integrated in the phospholipids. Most fatty acids are used for energy, but some, especially polyunsaturated fatty acids have other functions including interacting with cellular proteins, which in turn enter the nucleus and turn genes off and on. These genes are known to encode proteins important in controlling energy production from glucose and fat itself.

Fatty acids differ in their three-dimensional structure, which is determined by the chain-length of the molecule and the number of double bonds present. The most common dietary fatty acids consist of medium to long chains with no double bonds, resulting in a straight molecule. If a double bond is present then an angle of 120 degrees is produced. Thus, polyunsaturated fatty acids (PUFAs) have a completely different spatial resolution when compared to the saturated fatty acids. The differences in three dimensional structure between fatty acids means that while the PUFAs can act as signalling agents to the cell, switching gene transcription off or on, the saturated fatty acids are not recognised and have no effect. In the laboratory calorimeter all fats irrespective of their saturated or unsaturated nature generate 9 cal of energy per gram of fat, but when part of the diet, PUFAs give completely different net effects on metabolic energy production and weight gain compared to the saturated fatty acids. Thus, saturated fatty acids are the main source of energy in the human body, while PUFAs fulfil a different function. If energy expenditure is low such as with a sedentary lifestyle, high intake of saturated fatty acids correlates to increased body weight, diabetes, and cardiovascular disease. However, regular intake of PUFAs such as with seafood leads to a decrease of fat storage.

PUFAs are derived mainly from seeds and nuts or from fish oil. They may have their first double bond located either three or six carbon atoms away from the chain end. Thus, they are known either as omega-3 and omega-6 fatty acids, or n-3 and n-6 fatty acids. Humans cannot synthesise fatty acids with double bonds at the 3 or 6 location making these fatty acids essential dietary components. In certain cases both types of PUFA's may have the same action. One example is the effects of PUFA's on suppressing lipid synthesis in the liver while at the same time up-regulating fatty acid oxidation in the liver and skeletal muscle. It has also been demonstrated that PUFA's decrease the transcription of hepatic genes encoding glycolytic and lipogenic enzymes. The effect of the PUFA's on gene expression thus leads to increased metabolism and decreased fat storage, helping prevent weight gain. Energy production is mainly located to the mitochondria within the cell. The mitochondria do not differentiate between fatty acids as fuel and the energy produced is converted into ATP, which is used for a large number of energy dependent processes.

However, the PUFA's have also another production site for metabolic energy, namely the peroxisome also located inside the cell membrane. While the mitochondria produce the energy-rich ATP, peroxisomes probably are more active in the generation of heat.

The net effect is increased energy production as heat or metabolic energy instead of increasing the fat deposits. PUFA's are peroxisome proliferators increasing the amount and the activity of peroxisomes. While intake of saturated fats is strongly linked to obesity, diabetes, and cardiovascular disease, the ingestion of PUFA's particularly omega-3 fatty acids is associated with reduced adiposity, improved glucose turnover and a decrease in cardiovascular disease.

Nutritionists have been advising the substitution of saturated fatty acids with polyunsaturated fatty acids for the last 30 years. Now we are beginning to understand the molecular mechanisms underlying their beneficial action. In the meantime obesity is increasing together with the prevalence of cardiovascular disease.

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