Obesity and genetics
Obesity is a complex health issue that arises from the interplay of genetic, environmental, and lifestyle factors. Genetic research indicates that specific DNA variations influence body fat distribution and susceptibility to obesity. Studies have identified multiple genes, such as PTER and NPC1, that are linked to childhood and adult obesity, suggesting that genetics can account for a significant portion of obesity cases. However, the environment remains crucial, as lifestyle choices like dietary habits, physical activity levels, and socioeconomic factors play a dominant role in determining an individual's weight.
Risk factors for obesity include advancing age, sedentary behavior, and unhealthy eating patterns, such as high consumption of fast foods and carbohydrates. The symptoms of obesity extend beyond physical appearance to include medical complications like heart disease, diabetes, and mental health issues. Despite the challenges in treating obesity, a multifaceted approach involving dietary management, physical activity, behavior therapy, and, in some cases, medication or surgery can aid in weight loss. Prevention strategies emphasize the importance of maintaining a balanced diet and an active lifestyle, recognizing that both genetic predispositions and personal choices contribute to obesity risk. Understanding the genetic underpinnings of obesity can potentially lead to more targeted interventions and better health outcomes for individuals affected by this condition.
Obesity and genetics
DEFINITION Obesity is a very high amount of body fat. This fat buildup can have a negative impact on an individual’s health.
Risk Factors
Risk factors for obesity include advancing age, quitting smoking, working varied shifts, decreased activity, and a sedentary lifestyle. Other risk factors include an imbalance of excess calories versus decreased activity; a high level of fast-food intake; high alcohol consumption; eating foods with a high glycemic index, including carbohydrates, such as instant mashed potatoes, baked white potatoes, and instant rice; eating until full; and eating quickly.
Etiology and Genetics
Genetic determinants play a significant part in the development of obesity. In October 2010 researchers from an international consortium, the Genetic Investigation of Anthropometric Traits (GIANT), published two papers in Nature Genetics regarding their identification of thirteen new DNA regions of genetic variation associated with body fat distribution and eighteen new regions associated with increased susceptibility of obesity, adding to the fourteen obesity-associated regions already known. Alternative alleles at most of these genes may marginally increase one’s susceptibility to obesity, but environmental factors will still largely determine an individual’s overall body size.
Although the gene function is not well understood, genetic variations at the PTER gene are most strongly associated with childhood obesity and adult morbid obesity, according to a ten-year genome-wide association study of 1,380 Europeans with early onset childhood obesity and adult morbid obesity published in Nature Genetics in 2009. The same study found that these variations may contribute to as much as one-third of all childhood obesity and 20 percent of adult obesity. Another major player mentioned in the study was the NPC1 gene (at position 18q11.2), since its protein product seems to be involved in controlling appetite. The study estimated that allelic variations at this gene account for about 10 percent of childhood obesity and 14 percent of adult obesity. The MAF gene (at position 16q22–q23) encodes a protein that regulates the production of the hormones insulin and glucagon, key regulators of metabolism. The study estimated that variants at this locus account for about 6 percent of early onset childhood obesity and 16 percent of adult morbid obesity. The PRL gene (at position 6p22.3) specifies the hormone prolactin, which not only stimulates lactation in women but also helps regulate the amount of food consumed.
An excellent system to study obesity has been developed in mice, and these studies suggest that a protein known as leptin is particularly important for accelerating and reducing appetite. Leptin is specified by the LEP gene (at position 7q31), and four other genes have been identified whose protein products are necessary for proper functioning of leptin in the hypothalamus region of the brain: PCSK1, at position 5q15–q21; LEPR, at position 1q31; POMC, at position 2p23; and MC4R, at position 18q22. Mutations in any of these five genes can disrupt the normal leptin signaling pathway and result in obesity.
The 2010 GIANT Consortium report on obesity confirmed previous genome-wide association studies that found associations between body-mass index (BMI) and ten loci in or near the following genes: FTO, MC4R, TMEM18, GNPDA2, BDNF, NEGR1, SH2B1, ETV5, MTCH2, and KCTD15. The study also found eighteen new BMI-associated loci in or near the following genes: RBJ, GPRC5B, MAP2K5, QPCTL, TNNI3K, SLC39A8, FLJ35779, LRRN6C, TMEM160, FANCL, CADM2, PRKD1, LRP1B, PTBP2, MTIF3, ZNF608, RPL27A, and NUDT3.
Five years later, after an even larger study involving three hundred thousand individuals, GIANT announced that further progress had been made in the area through the discovery of more than 140 loci that contribute to different obesity traits. In addition to supporting the notion that obesity is linked to several genes rather than a single gene, this research revealed that the locations could be involved with neural processes connected to appetite control and energy use. The hope remained that scientists would be able to use the information obtained from the study to better understand how the genetic variations can increase the susceptibility to gain weight and subsequently come up with more targeted prevention and treatment methods.
A study of variations in the mitochondrial DNAs (deoxyribonucleic acids) of obese members of the Pima tribe of American Indians suggested that these mitochondrial DNA mutations affect enzymes in the mitochondrial respiratory chain and increase metabolic efficiency. The researchers concluded that an increased metabolic efficiency might have been advantageous at one time, since that perhaps would have allowed the Pimas to better survive the harsh dietary environment of the Sonoran Desert. In the twenty-first century, with caloric overconsumption the norm, an increased efficiency may be unfavorable and contribute to the high incidence of obesity among the population.
Symptoms
Symptoms of obesity include increased weight, thickness around the midsection, and obvious areas of fat deposits. Complications of untreated obesity include decreased energy, heart disease, high blood pressure, high blood pressure during pregnancy, type 2 diabetes, gallstones, worsening arthritis symptoms, and an increased risk of certain cancers. Additional symptoms include gout, infertility, sleep apnea, poor self-image, depression, urinary incontinence, and the increased risk of death for individuals who have increased waist circumferences and waist-to-hip ratios.
Screening and Diagnosis
Obesity is diagnosed by visual exam and body measurements using height and weight tables, body mass index, a caliper to measure body folds, waist-to-hip ratio measurements, and water-displacement tests. The doctor may also order blood tests to rule out other medical conditions that may cause excess body weight.
Treatment and Therapy
Obesity is difficult to treat. Its treatment is affected by cultural factors, personal habits, lifestyle, and genetics. There are many different treatment approaches. Patients should talk to their doctors or ask for a referral to a specialist; the doctor and specialist can help develop the best treatment plan.
Plans for weight loss may include keeping a food diary, in which patients track everything they eat or drink. Patients should ask their doctors about an exercise program, which is another treatment option. Individuals can add bits of physical activity throughout their days, take stairs instead of elevators, and park a little farther away. Patients can also limit the amount of time they spend watching television and using the computer; this is important for children.
A dietitian can help patients with their total calorie intake goal, which is based on their current weights and weight loss goals. Portion size also plays an important role; using special portion control plates may help patients succeed.
The doctor may recommend that patients reduce saturated and trans fats, limit the amount of refined carbohydrates they eat, and keep fat intake under 35 percent of the total calories eaten daily. Behavior therapy may help patients understand when they tend to overeat, why they tend to overeat, and how to combat overeating habits.
Research on the effectiveness of weight-loss programs is limited. These programs do seem to work for some people. Some studies suggest that a partner or group may help a patient improve his or her diet and fitness.
Weight loss medications include sibutramine (Meridia), orlistat (Xenical), metformin (Glucophage), orlistat (Alli, Xenical), and phentermine (Adipex-P, Ionamin, Pro-Fast). Semaglutide (Wegovy) received Federal Drug Administration (FDA) approval in 2021. Some medications have led to serious health complications and side effects are not uncommon. Patients should not use over-the-counter or herbal remedies without talking to their doctors.
Surgical procedures reduce the size of the stomach and rearrange the digestive tract. The smaller stomach can hold only a tiny portion of food at a time. Surgical operations include gastric bypass and laparoscopic gastric banding. These procedures can have serious complications, and they are an option only for people who are dangerously overweight.
Prevention and Outcomes
Preventing obesity can be difficult. There are many factors that influence an individual’s weight. General recommendations include talking to a doctor or a dietician about an appropriate number of calories to eat per day and eating a diet with no more than 35 percent of daily calories from fat. Individuals can follow an appropriate exercise program; limit the amount of time they spend doing sedentary activities, including watching television or using the computer; and talk to their doctors or an exercise professional about working activity into their daily lives. Individuals can also ask a dietitian for help planning a diet that will help them maintain a healthy weight or lose weight if necessary. In addition, individuals can learn to eat smaller portions of food; most Americans eat portions that are too large.
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