Research has long established that genetics play a significant role in obesity. Scientists from the University of Exeter Medical School have identified a genetic variant linked to the absence of a specific blood group, which may predispose individuals to obesity or being overweight. This genetic variant involves the missing SMIM1 gene, which researchers believe could be treated using an existing drug for thyroid dysfunction.
While lifestyle factors are known contributors to obesity, genetics are also influential. For example, a study earlier this year suggested that children may inherit obesity from their parents, and a study published in February 2023 linked 21 genes associated with Alzheimer’s disease to obesity. Now, researchers at the University of Exeter Medical School have discovered that individuals missing the SMIM1 gene due to a genetic variant are more likely to struggle with obesity or being overweight.
The Role of the SMIM1 Gene In their study, published in the journal Med, researchers analyzed genetic data from approximately 500,000 people in the UK Biobank and four other cohorts to identify those with a genetic variant that deactivates the SMIM1 gene. “SMIM1 encodes a 68-amino-acid protein that protrudes from the red cell membrane,” explained Mattia Frontini, PhD, associate professor of cell biology at the University of Exeter Medical School and lead author of the study. “There is little known about this gene, but it belongs to a family of genes that encode short transmembrane proteins.” The discovery of the SMIM1 gene and its faulty version ten years ago was initially driven by the need to develop a genetic test for a blood group known as Vel, which is difficult to type using traditional methods. Subsequent research revealed that variations in these genes are associated with minor changes in red blood cell parameters.
Impact on Obesity Using genetic and blood sample data, Frontini and his team found that people with two faulty copies of the SMIM1 gene—about 1 in 5,000 individuals—are more likely to be overweight. These individuals have altered blood lipids, use less energy despite similar caloric intake, and store the excess as fat. Additionally, they exhibit higher levels of fat in the blood, signs of fat tissue dysfunction, increased liver enzymes, and lower levels of thyroid hormones. Frontini noted that the SMIM1 gene affects the hypothalamus-pituitary-thyroid axis, which controls hormone production. The absence of SMIM1 causes a mild form of hypothyroidism, leading to reduced resting energy expenditure. As a result, people with this genetic variant use less energy for the same caloric intake, causing excess energy to be stored as fat. In the UK, nearly 2% of the population receives thyroid supplementation, which is an effective and affordable treatment. “For the first time, we linked this gene [SMIM1] and its product to metabolism control. Further research is needed to determine if the gene is part of a novel pathway or part of known pathways that control metabolism,” Frontini said.
Genetic Basis of Obesity Hans J. Schmidt, MD, director of the Center for Weight Loss and Metabolic Health and chief of Minimally Invasive and Bariatric Surgery at Hackensack University Medical Center in New Jersey, agrees that genetics can significantly influence obesity. He pointed out that some people easily gain weight while others do not, regardless of their diet, suggesting a strong genetic component. “This study shows evidence of a link between a loss of function of the SMIM1 gene and excess weight,” Schmidt said. “The SMIM1 gene codes for a protein involved in regulating fat metabolism. In patients without this gene function, reduced energy expenditure leads to weight gain.” Schmidt suggested that further research should explore associations between other genetic traits and weight to better understand the genetic basis of obesity and improve treatment strategies. Mir Ali, MD, a board-certified bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, also found the study compelling. He emphasized that obesity is multifactorial, with many genes contributing to weight gain. Identifying genetic variants predisposing individuals to obesity could enable early intervention and the development of targeted treatments.
While lifestyle factors are known contributors to obesity, genetics are also influential. For example, a study earlier this year suggested that children may inherit obesity from their parents, and a study published in February 2023 linked 21 genes associated with Alzheimer’s disease to obesity. Now, researchers at the University of Exeter Medical School have discovered that individuals missing the SMIM1 gene due to a genetic variant are more likely to struggle with obesity or being overweight.
The Role of the SMIM1 Gene In their study, published in the journal Med, researchers analyzed genetic data from approximately 500,000 people in the UK Biobank and four other cohorts to identify those with a genetic variant that deactivates the SMIM1 gene. “SMIM1 encodes a 68-amino-acid protein that protrudes from the red cell membrane,” explained Mattia Frontini, PhD, associate professor of cell biology at the University of Exeter Medical School and lead author of the study. “There is little known about this gene, but it belongs to a family of genes that encode short transmembrane proteins.” The discovery of the SMIM1 gene and its faulty version ten years ago was initially driven by the need to develop a genetic test for a blood group known as Vel, which is difficult to type using traditional methods. Subsequent research revealed that variations in these genes are associated with minor changes in red blood cell parameters.
Impact on Obesity Using genetic and blood sample data, Frontini and his team found that people with two faulty copies of the SMIM1 gene—about 1 in 5,000 individuals—are more likely to be overweight. These individuals have altered blood lipids, use less energy despite similar caloric intake, and store the excess as fat. Additionally, they exhibit higher levels of fat in the blood, signs of fat tissue dysfunction, increased liver enzymes, and lower levels of thyroid hormones. Frontini noted that the SMIM1 gene affects the hypothalamus-pituitary-thyroid axis, which controls hormone production. The absence of SMIM1 causes a mild form of hypothyroidism, leading to reduced resting energy expenditure. As a result, people with this genetic variant use less energy for the same caloric intake, causing excess energy to be stored as fat. In the UK, nearly 2% of the population receives thyroid supplementation, which is an effective and affordable treatment. “For the first time, we linked this gene [SMIM1] and its product to metabolism control. Further research is needed to determine if the gene is part of a novel pathway or part of known pathways that control metabolism,” Frontini said.
Genetic Basis of Obesity Hans J. Schmidt, MD, director of the Center for Weight Loss and Metabolic Health and chief of Minimally Invasive and Bariatric Surgery at Hackensack University Medical Center in New Jersey, agrees that genetics can significantly influence obesity. He pointed out that some people easily gain weight while others do not, regardless of their diet, suggesting a strong genetic component. “This study shows evidence of a link between a loss of function of the SMIM1 gene and excess weight,” Schmidt said. “The SMIM1 gene codes for a protein involved in regulating fat metabolism. In patients without this gene function, reduced energy expenditure leads to weight gain.” Schmidt suggested that further research should explore associations between other genetic traits and weight to better understand the genetic basis of obesity and improve treatment strategies. Mir Ali, MD, a board-certified bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, also found the study compelling. He emphasized that obesity is multifactorial, with many genes contributing to weight gain. Identifying genetic variants predisposing individuals to obesity could enable early intervention and the development of targeted treatments.
About this article
From the Medical Directory library. For advice about your own health, speak to your healthcare professional.
JOIN THE CONVERSATION
No comments yet. Add a thoughtful question or comment about this article.