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Metabolism Fact vs Fiction: It’s in my genes!

Have you ever thought to yourself, “I can’t lose weight because of my genetics”? To date, more than 400 different genes have been implicated in the causes of overweight or obesity, but only a handful appear to be major players. Genes contribute to the causes of obesity in many ways, by affecting appetite, satiety (the sense of fullness), metabolism, food cravings, body-fat distribution, and the tendency to use eating as a way to cope with stress. The strength of the genetic influence on weight disorders varies quite a bit from person to person. Research suggests that for some people, genes account for just 25% of the predisposition to be overweight, while for others the genetic influence is as high as 70% to 80%.

Monogenic vs Polygenic Obesity

Now body fat level varies from person to person and some people have always tended to carry a bit more body fat than others. So why is this? Evidence from animal models, human linkage studies, twin studies, and association studies of large populations suggests that this variation in our susceptibility to obesity has a genetic component.

We have classically divided obesity in two broad categories: monogenic obesity and polygenic obesity, Several rare forms of obesity result from spontaneous mutations in single genes, so-called monogenic mutations. Such mutations have been discovered in genes that play essential roles in appetite control, food intake, and energy homeostasis-primarily, in genes that code for the hormone leptin, the leptin receptor, pro-opiomelanocortin, and the melanocortin-4 receptor, among others.

Polygenic obesity, or common obesity, is thought to be affected by many genes. And common obesity has a strong relationship with our environment or our behaviors. We are going to stick with common obesity for our discussion.

There isn’t a single gene responsible, but rather hundreds that are linked to appetite, glucose absorption, and metabolism. These genes can be put into four broad categories:

1. Regulation of food intake by molecular signaling in the hypothalamus and hindbrain by signals originating in adipose tissue, gut and other organs

2. Regulation of adipocyte differentiation and fat storage

3. Regulation of spontaneous exercise activity

4. Effect on basal and postprandial thermogenesis.

FTO Gene

Let’s look at one particular gene, the FTO gene, that is getting a lot of study. People carrying the FTO gene are inclined to higher energy intake foods like fat or proteins, reduced satiety, resulting in overeating, and many even lose control when eating. Individuals with high levels of the FTO gene may be more likely to become obese due to increased production of fat cells, which would expand storage capacity and favor the deposition of energy over energy burning. Research is all over the board on how many people carry this gene ranging for 16-43%. The FTO gene comes in two forms - a low obesity-risk variant and a high-obesity risk variant. Each person inherits two copies of this gene, one from each parent. Among people who inherit two high-risk copies, the risk of obesity is thought to be increased by around 70%. However, people with the FTO gene can lower their risk of obesity by 27% if they exercise regularly.

How do I know if my genes are affecting me?

How do we know if our genes really do affect our ability to lose weight? Ideally a genome assessment would be completed, but that is not realistic. Genes are probably a significant contributor to your obesity if you have most or all of the following characteristics:

  • You have been overweight for much of your life.

  • One or both of your parents or several other blood relatives are significantly overweight. If both of your parents have obesity, your likelihood of developing obesity is as high as 80%.

  • You can't lose weight even when you increase your physical activity and stick to a low-calorie diet for many months.

Genes are probably a lower contributor for you if you have most or all of the following characteristics:

  • You are strongly influenced by the availability of food.

  • You are moderately overweight, but you can lose weight when you follow a reasonable diet and exercise program.

  • You regain lost weight during the holiday season, after changing your eating or exercise habits, or at times when you experience psychological or social problems.

These circumstances suggest that you have a genetic predisposition to be heavy, but it's not so great that you can't overcome it with some effort. People with only a moderate genetic predisposition to be overweight have a good chance of losing weight on their own by eating fewer calories and getting more vigorous exercise more often. These people are more likely to be able to maintain this lower weight.

Are we doomed by our genes?

Even if you express these genes, this should not be viewed as a lifetime obesity sentence or final destination. They are merely risk factors, and we should never be discouraged by family histories or genetic makeup. What’s increasingly clear from these early findings is that genetic factors identified so far make only a small contribution to obesity risk-and that our genes are not our destiny. Genetic changes are unlikely to explain the rapid spread of obesity around the globe. That’s because the “gene pool” or the frequency of different genes across a population has remained fairly stable for many generations. It takes a long time for new mutations to spread. So, if our genes have stayed largely the same, what has changed over the past 40 years of rising obesity rates?

Our environment!: the physical, social, political, and economic surroundings that influence how much we eat and how active we are. Most people probably have some genetic predisposition to obesity, depending on their family history and ethnicity. Moving from genetic predisposition to obesity itself generally requires some change in diet, lifestyle, or other environmental factors.

Environmental Factors

What are environmental factors? The ready availability of food at all hours of the day and in places that once did not sell food, such as gas stations, pharmacies, and office supply stores; a dramatic decrease in physical activity during work, domestic activities, and leisure time, especially among children; increased time spent watching television, using computers, and performing other sedentary activities; and the influx of highly processed foods, fast food, and sugar-sweetened beverages, along with the ubiquitous marketing campaigns that promote them. All these factors contribute to the increase risk of obesity.

Having a better understanding of the genetic contributions to obesity-especially common obesity-and gene-environment interactions will generate a better understanding of the causal pathways that lead to obesity. It is important to remember that overall, the contribution of genes to obesity risk is small, while the contribution of our toxic food and activity environment is high. I love the following saying: Genetics loads the gun, environment pulls the trigger.

Next month we will discuss hormonal influences and our metabolism.

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