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Genes and Gene Products Associated with Body Weight Regulation

The Role of Genetics in Obesity: A Simplified Overview

Obesity is a complex condition. Its roots run deep into our genes, and yet, our environment and lifestyle choices also play a significant role. Think of it like a garden – our genes are the seeds, with the potential to grow, but how they grow depends on the environment they are in – the soil, the weather, the care they receive.

Scientists use a tool called a Genome-Wide Association Study (GWAS) to study the genetic roots of obesity. It's like a detective tool that scans the DNA, our genetic blueprint, to find specific genes linked to obesity.

Over the years, this tool has helped identify more than 250 regions in our DNA that are associated with obesity1. However, this is just the tip of the iceberg. Each of these regions contributes a small fraction to the risk of obesity, and there are likely many more still undiscovered.

Some genes have a more significant impact. For example, mutations in the MC4R gene, which plays a crucial role in regulating our appetite and energy use, are the most common genetic cause of severe obesity2. People with these mutations may struggle with obesity from a young age due to an insatiable appetite.

Besides the direct genetic influence, our genes also interact with the environment, a concept known as "gene-environment interaction". Let's go back to our garden analogy. Even the most robust seeds may not grow in poor soil or extreme weather. Similarly, a person with a genetic predisposition to obesity might maintain a healthy weight by living in an environment that encourages physical activity and a balanced diet.

Moreover, our lifestyle choices can also influence how our genes work through a process called "epigenetics". It's like installing software updates on your computer that changes how it operates without altering the hardware. For instance, a high-fat diet can trigger changes in our genes that make us more prone to weight gain3.

So, what does this all mean for you? Understanding the role of genetics in obesity can help tailor more effective treatment strategies. For instance, people with mutations in the MC4R gene may benefit from drugs specifically targeting this pathway2.

In conclusion, obesity is a complex interplay of our genetic makeup and our environment. It's not merely a matter of willpower. By understanding this, we can remove the stigma associated with obesity and work towards more personalized and effective treatment strategies.

References:

Footnotes
  1. Locke AE, Kahali B, Berndt SI, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518(7538):197-206.

  2. Clement K, Biebermann H, Farooqi IS, et al. MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency. Nat Med. 2018;24(5):551-555. ↩2

  3. Dick KJ, Nelson CP, Tsaprouni L, et al. DNA methylation and body-mass index: a genome-wide analysis. Lancet. 2014;383(9933):1990-1998.

List of Obesity-Related Human Genes

Acetyl-CoA carboxylase beta

ACACB

Name of Protein

Function

Acetyl-CoA carboxylase beta

Regulates fatty acid oxidation and energy metabolism

Year Discovered

1994

Adenylate cyclase 3

ADCY3

Name of Protein

Function

Adenylate cyclase 3

Regulates cAMP signaling| involved in energy homeostasis

Year Discovered

1997

Adiponectin receptor 1

ADIPOR1

Name of Protein

Function

Adiponectin receptor 1

Regulates glucose and lipid metabolism in response to adiponectin

Year Discovered

2003

Adiponectin receptor 2

ADIPOR2

Name of Protein

Function

Adiponectin receptor 2

Regulates glucose and lipid metabolism in response to adiponectin

Year Discovered

2003

Beta-2 adrenergic receptor

ADRB2

Name of Protein

Function

Beta-2 adrenergic receptor

Regulates lipolysis and thermogenesis in adipose tissue

Year Discovered

1987

Beta-3 adrenergic receptor

ADRB3

Name of Protein

Function

Beta-3 adrenergic receptor

Regulates lipolysis and energy expenditure

Year Discovered

1989

Agouti-related protein

AGRP

Name of Protein

Function

Agouti-related protein

Regulates appetite and energy homeostasis

Year Discovered

1997

Angiopoietin-like 4

ANGPTL4

Name of Protein

Function

Angiopoietin-like 4

Regulates lipid metabolism and energy homeostasis

Year Discovered

2000

Brain-derived neurotrophic factor

BDNF

Name of Protein

Function

Brain-derived neurotrophic factor

Promotes neuronal survival and differentiation| regulates energy balance

Year Discovered

1989

Bone morphogenetic protein 8B

BMP8B

Name of Protein

Function

Bone morphogenetic protein 8B

Regulates energy expenditure and thermogenesis

Year Discovered

1997

Cocaine- and amphetamine-regulated transcript protein

CARTPT

Name of Protein

Function

Cocaine- and amphetamine-regulated transcript protein

Regulates appetite and energy homeostasis

Year Discovered

1995

CDK5 regulatory subunit-associated protein 1-like 1

CDKAL1

Name of Protein

Function

CDK5 regulatory subunit-associated protein 1-like 1

Regulates insulin secretion and energy homeostasis

Year Discovered

2007

Cadherin EGF LAG seven-pass G-type receptor 2

CELSR2

Name of Protein

Function

Cadherin EGF LAG seven-pass G-type receptor 2

Regulates cell adhesion and signaling| implicated in energy homeostasis

Year Discovered

1999

Cytoplasmic polyadenylation element binding protein 4

CPEB4

Name of Protein

Function

Cytoplasmic polyadenylation element binding protein 4

Regulates mRNA polyadenylation and translation| implicated in energy homeostasis

Year Discovered

2009

Type 2 iodothyronine deiodinase

DIO2

Name of Protein

Function

Type 2 iodothyronine deiodinase

Regulates thyroid hormone activation and energy metabolism

Year Discovered

1990

ELOVL fatty acid elongase 6

ELOVL6

Name of Protein

Function

ELOVL fatty acid elongase 6

Regulates fatty acid elongation and metabolism

Year Discovered

2000

Fibroblast growth factor 21

FGF21

Name of Protein

Function

Fibroblast growth factor 21

Regulates glucose and lipid metabolism

Year Discovered

2000

Fibroblast growth factor receptor 2

FGFR2

Name of Protein

Function

Fibroblast growth factor receptor 2

Regulates cell growth and differentiation| implicated in energy metabolism

Year Discovered

1990

Fat mass and obesity-associated protein

FTO

Name of Protein

Function

Fat mass and obesity-associated protein

Regulates energy homeostasis and body weight

Year Discovered

2007

Glutamate decarboxylase 2

GAD2

Name of Protein

Function

Glutamate decarboxylase 2

Regulates GABA synthesis| involved in energy homeostasis

Year Discovered

1987

Growth hormone secretagogue receptor

GHSR

Name of Protein

Function

Growth hormone secretagogue receptor

Regulates appetite and energy homeostasis

Year Discovered

1996

Glucose transporter type 4

GLUT4

Name of Protein

Function

Glucose transporter type 4

Regulates glucose uptake and energy homeostasis

Year Discovered

1989

Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3

GNB3

Name of Protein

Function

Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3

Regulates signal transduction pathways| involved in energy balance and metabolism

Year Discovered

1994

Insulin receptor substrate 1

IRS1

Name of Protein

Function

Insulin receptor substrate 1

Mediates insulin signaling| involved in energy metabolism

Year Discovered

1992

Potassium voltage-gated channel subfamily J member 11

KCNJ11

Name of Protein

Function

Potassium voltage-gated channel subfamily J member 11

Regulates insulin secretion and energy homeostasis

Year Discovered

1995

Potassium channel tetramerization domain-containing 15

KCTD15

Name of Protein

Function

Potassium channel tetramerization domain-containing 15

Regulates neural crest formation| implicated in adipogenesis

Year Discovered

2008

Leptin

LEP

Name of Protein

Function

Leptin

Regulates energy intake and expenditure

Year Discovered

1994

Hormone-sensitive lipase

LIPE

Name of Protein

Function

Hormone-sensitive lipase

Regulates lipolysis and energy homeostasis

Year Discovered

1964

Melanocortin 4 receptor

MC4R

Name of Protein

Function

Melanocortin 4 receptor

Regulates energy balance and appetite

Year Discovered

1993

Mitochondrial carrier 2

MTCH2

Name of Protein

Function

Mitochondrial carrier 2

Regulates mitochondrial function and energy homeostasis

Year Discovered

2000

Neuromedin B

NMB

Name of Protein

Function

Neuromedin B

Neuropeptide| involved in energy homeostasis and feeding behavior

Year Discovered

1985

Neuropeptide Y

NPY

Name of Protein

Function

Neuropeptide Y

Regulates appetite and energy homeostasis

Year Discovered

1982

Neurexin-3

NRXN3

Name of Protein

Function

Neurexin-3

Regulates synaptic function| implicated in energy homeostasis

Year Discovered

1995

Proprotein convertase subtilisin/kexin type 1

PCSK1

Name of Protein

Function

Proprotein convertase subtilisin/kexin type 1

Regulates processing of prohormones| involved in energy homeostasis

Year Discovered

1993

Perilipin 1

PLIN1

Name of Protein

Function

Perilipin 1

Regulates lipid storage and lipolysis in adipocytes

Year Discovered

1996

Perilipin 4

PLIN4

Name of Protein

Function

Perilipin 4

Regulates lipid storage and lipolysis in adipocytes

Year Discovered

2004

Patatin-like phospholipase domain-containing protein 2

PNPLA2

Name of Protein

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