The World Obesity Federation reports a ‘growing and disturbing global health crisis,’ with 2.7 billion overweight and obese adults predicted by 2025, many of whom are likely to end up needing medical care. That means a third of the global population will be overweight or obese. In the UK, more than a quarter of adults (27%) were obese in 2014 and that will rise to 34% by 2025.
Body mass index is the most common measure of obesity and is a ratio between weight and height. It is imperfect on an individual basis, because it does not allow for muscle as opposed to fat, but it can give an assessment of population risk. BMI of 25 to 29 is considered to be overweight, while over 30 is obese. Many people assume you need to be really overweight to be at risk but when you hit a BMI of over 25, for developing health condition including diabetes, where there is a 60% increase in cases in the last decade in the UK, heart disease and other life-threatening conditions.
What can genes our tell us about our risk of obesity?
Certain genetic variants are associated with weight-loss resistance, increased risk of obesity and slower weight loss outcomes, predispositions to crave certain foods, snack more often and having a reduced feeling of satiety. Let’s explore a few of these genes.
The Fat-mass-and-obesity-associated (FTO) gene can impact weight management and body composition. FTO is present at high levels in several metabolically active tissues and is associated with metabolic rate, energy expenditure and balance. It is expressed throughout the body and in the brain, particularly in the hypothalamus which is concerned with the regulation of arousal, appetite and the endocrine systems. FTO plays a role in appetite regulation and that is associated with energy expenditure, energy intake, and diminished satiety. A genetic variant is associated with increased BMI, body fat percentage and waist measurement, especially in people with a sedentary lifestyle. People with the variants may have a reduced ability to feel full after eating, and likely to overeat. Overweight people are at an increased risk for insulin resistance and diabetes, especially when there is an unhealthy diet.
The Melanocortin-4 Receptor (MC4R) gene is involved in the regulation of our appetite. People with the MC4R variant are deficient in the MC4R protein and can show increased food intake, obesity and hyperinsulinaemia. Recent research shows those carrying the genetic variant can have an increased preference for high fat foods and decreased preference for sugar foods.
The Fatty acid binding protein 2 (FABP2) is located in the small intestine epithelial cells and involved in lipid absorption and metabolism. A genetic variant results in a threonine at position 54 instead of alanine and is associated with increased fat absorption, insulin resistance, obesity and type 2 diabetes. FABP2 is also associated with higher total cholesterol and LDL and lower HDL in the presence of a high saturated fat diet. Research has indicated that reducing saturated fats and supplementation with EPA may be beneficial to those with hypertriglyceride profile carrying the T allele.
Peroxisome Proliferator-Activated Receptor (PPARG) is the “Thrifty gene”. It was called this because it helps us store fat into fat cells and survive the winter. It does this by working on both fatty acids and glucose in the blood and pushing them into fat cells. As a result, in times of plenty, PPARG can cause obesity if we consume a typical Western diet with too much fat and sugar.
Apolipoprotein A2 (APOA2) gene directs the body to produce apolipoprotein, which plays a role in the body’s ability to utilise different kinds of fat. The gene interacts with saturated fat to influence energy balance. People with genetic variants are at a higher risk of developing obesity when consuming a diet high in saturated fats.
Transcription factor 7-Like 2 (TCF7L2) switches on several other genes within the cell to initiate receiving insulin to the receptor and sugar to the cell. The TCF7L2 is a significant gene variant associated with increased risk for insulin resistance and Type-2 diabetes. People with this variant could be resistant to weight loss and a reduction in sugars and refined carbohydrates may be beneficial.
Epigenetics: The effect of our environment
Genes are however only half the picture; the rest lies in a person’s environment (lifestyle) and its effect on gene expression. For example, current research shows that specific dietary and physical activity recommendations can help with weight loss and weight management in people who have the FTO variants. By walking daily for 30 minutes that risk can be reduced by 30 percent. By watching the diet, eating loads of leafy greens, along with the exercise, the risk is lowered by 50 percent.
Much more work is needed to prevent tens of thousands of cases of obesity-related diseases over the next 25 years. Weight management services are typically commissioned by the local authority and it should be possible to help people get a grip on their understanding of their genetic risks alongside their current lifestyle contributing to the risk. By informing and intervening with a personalised approach we can help them to manage their weight loss for longer periods of time and therefore retain better health.
