DNA Weight Loss Test

Obesity 

Obesity is a worldwide problem that affects all ages and ethnicities. According to the World Health Organization, obesity affects 600 million adults (13% of the world’s adult population) and 42 million children under the age of five years (2015 report). It affects both genders, but is more common in women. 

Obesity is defined by body mass index (BMI), which is determined by dividing an individuals mass (in kilograms) by the square of their height (in metres). A “clinically obese” individual has a BMI between 30 and 39.99, while a “morbidly obese” value is greater than 40. Individuals who fall into these categories are likely to have specific genetic variations that influence their body weight. 

What are the risks of obesity?
The accumulation of body fat in obese individuals has a significant negative impact on their health. Obese individuals have a higher risk of multiple health problems, particularly cardiovascular issues, type 2 diabetes, liver disease, obstructive sleep apnea, several cancers, asthma and osteoarthritis. Due to these health complications, obesity is associated with a reduced life expectancy (averaging 6 – 7 years lower than normal weight individuals).

What factors influence obesity risk?
Obesity is generally due to a combination of excess calories, lack of physical exercise and genetic susceptibility. The increasing rate of obesity is likely due to an easily accessible (and often unhealthy) food source, increased reliance on vehicular transport, mechanized manufacturing and labor saving technology (e.g. washing machines). Genetic changes can also influence hormonal and neuronal signaling pathways, digestion and metabolism of dietary components, desire to overeat and the motivation to exercise. 

Preventing Obesity
Diet and exercise modifications are the best way to prevent and overcome obesity. Limiting the intake of foods high in fat and sugars, and increasing the intake of dietary fiber, can greatly improve the likelihood of reducing body fat and maintaining a healthy body weight. Medications and surgical procedures may also be required. The genetic analysis available here also provides individuals with an understanding of their own genetic factors that influence the risk of obesity, and allows a personalized intervention for more effective treatment and prevention of obesity.

What genes affect obesity risk?

Energy intake and satiety – the FTO and SH2B1 genes
An individual’s energy intake is one of the major influences of obesity risk. There are various sources of energy – e.g. protein and fat – and the type of energy source affects people in different ways. Satiety is the feeling of fullness that is normally achieved after eating. Hunger and satiety are influenced by two hormones – the “hunger hormone” ghrelin and the “satiety hormone” leptin. If these hormones are out of balance, or a person has a reduced sensitivity to leptin, they can have a delayed or diminished satiety and may not feel full until they have consumed large quantities of food.

• The FTO gene encodes the fat mass and obesity associated protein. The functions of the FTO protein are not fully understood, but specific FTO variants are known to influence a person’s energy intake, diet impact and satiety. There are three common variants in the FTO gene that strongly influence the risk of obesity, but this genetic influence can be modified by diet and exercise changes. 
• The SH2B1 gene encodes an important regulator for the maintenance of normal body weight. A variation of the SH2B1 gene has been shown to increase the risk of obesity in several different populations by affecting the signaling pathway that transmits the leptin satiety signal.

Snacking and overeating – the MC4R and NMB genes
Adequate appetite suppression is an important part of maintaining a healthy body weight. However, many people have decreased appetite suppression and tend to crave food more often and continuously snack. Other people suffer from food disinhibition, which is a tendency to overeat, often despite a feeling of fullness. Healthy snacks are beneficial in small quantities to help control hunger cravings and boost energy levels. Unfortunately, many people take the convenient, unhealthy snack option instead.

• The MC4R gene encodes the melanocortin 4 receptor, which is highly expressed in the hypothalamus. Normally this receptor binds the α-MSH melanocortin hormone, leading to appetite suppression and increased metabolism. A genetic variation near the MC4R gene disrupts this appetite suppression and is strongly linked to an increased risk of excessive snacking and overeating, leading to obesity.
• The NMB gene encodes neuromedin beta – a protein that has many biological effects that can affect food intake and obesity risk. A variation of the NMB gene is associated with an increased likelihood of food disinhibition. Individuals with this variant have a tendency to overeat or continuously snack, leading to an increased risk of obesity. 

Exercise motivation – the BDNF gene
Adequate physical activity is essential for a healthy body and mind. However, many people lack the motivation for physical exercise or have a low exercise tolerance, increasing their risk of obesity and other health problems.

• The BDNF gene encodes a neurotrophin, which has an important role in energy balance regulation in the brain. A variation of the BDNF gene influences energy balance and obesity risk by altering an individual’s motivation to exercise.

Saturated fat metabolism – the APOA2 gene
Saturated fats are found in high quantities in red meat and dairy products. They are considered the “bad fats” because they are linked to various health problems, including diabetes, cardiovascular disease and obesity.

• The APOA2 gene encodes apolipoprotein A-II, which is one of the most abundant proteins found in high-density lipoprotein (HDL) particles. A variation of the APOA2 gene affects how an individual responds to their saturated fat intake. On a low saturated fat diet, the increased risk genotype does not alter the risk of obesity. However, on a high saturated fat diet (e.g. high dairy or red meat consumption), the increased risk genotype is associated with obesity and poor diet choices.

Starch digestion – the AMY1 gene
Starch is a major carbohydrate in our diet and is found in high levels in potatoes, rice, wheat and corn. Amylase is the enzyme responsible for starch digestion. Several studies have shown a link between decreased amylase levels and a decreased ability to efficiently digest starch, leading to an increased obesity risk.

• The AMY1 gene encodes for the salivary form of the amylase enzyme. One variation of the AMY1 gene is associated with decreased amylase levels. This results in a reduced ability to digest starch and an increased obesity risk, when on a high-starch diet.

Fatty acid uptake – the FABP2 gene
Fatty acids are a major energy source for many cells in our body. Fatty acids can be saturated (the predominant form in animal sources such as butter) or the healthier unsaturated form found in plant oils and fatty fish.

• The FABP2 gene encodes an intestinal protein that is involved in the absorption and metabolism of fatty acids from the diet. A variation of the FABP2 gene alters the uptake and processing of fatty acids and is associated with an increased risk of obesity, but only on a diet high in unhealthy saturated fats.

Adiponectin levels – the ADIPOQ Gene
Adiponectin is an abundant protein hormone that is involved in the regulation of glucose levels and fatty acid metabolism. Adiponectin is produced by adipose tissue (fat tissue) and is released into the blood stream to signal muscles to utilize energy from fat stores. Several studies have identified an association between lower adiponectin levels and an increased risk of obesity.

• The ADIPOQ gene encodes the adiponectin protein, which is an important regulator of glucose levels and fatty acid metabolism. Adiponectin levels are influenced by dietary intake, as well as genetic polymorphisms in the ADIPOQ gene. There are three common variations in the ADIPOQ gene that influence the risk of obesity and the likelihood of regaining weight if an individual does not maintain a low-calorie diet.

Physical exercise response – the ADRB2 gene 
Epinephrine is a hormone and neurotransmitter more commonly known as adrenaline. This hormone plays an important role in the fight-or-flight response, but also helps to regulate multiple other physiological responses. Epinephrine affects lipolysis (the breakdown of lipids) and fatty acid oxidation (utilization of fatty acids for energy) through interactions with the beta-2 adrenergic receptor (ADRB2).

• The ADRB2 gene encodes the beta-2 adrenergic receptor. This receptor interacts with epinephrine (adrenaline) to mediate a diverse range of physiological responses, including the generation of glucose for energy, lipolysis, fatty acid oxidation and insulin secretion. A variation in the ADRB2 gene is linked to obesity risk and weight loss in response to exercise and carbohydrate intake, particularly in women.

Metabolic circadian rhythm – the CLOCK gene
Circadian rhythms are roughly 24-hour cycles that occur endogenously, but can also be modulated by external cues (e.g. sunlight). The sleep-wake cycle is one example of a circadian rhythm. Metabolism-related functions also follow a circadian rhythm.

• The CLOCK gene encodes a regulator of circadian rhythms. The disruption of the CLOCK regulator can affect the circadian patterning of metabolism-related functions, leading to an increased risk of obesity.