Why study genetics of obesity?

Some breeds of dog are prone to obesity.  That suggests genetics play a part in why some dogs become obese.  These predispositions are well recognised and can’t be explained by owner factors alone.

That mirrors the case in humans, where 40-70% of person-to-person variation in obesity risk is down to genetics, independent of family or social circumstance.

There has been lots of research in rodents and humans about how genes cause obesity.  This short video is a provoking and light hearted introduction to the importance of obesity genetics.

The Hunger Genes

The majority of genes linked to obesity affect appetite.  Sensations of hunger, fulness and even food choice are all controlled in an area of the brain called the hypothalamus.  The hypothalamus integrates messages from the gut, circulation, fat and conscious parts of the brain to turn hunger up or down.  You can get more information about how energy balance is physiologically controlled on our website here or in scientific review articles here.

Studies of humans and mice have shown a molecular chain of events in the hypothalamus called the leptin-melanocortin pathway is central to appetite control.  (GOdogs have also discovered it is very important in Labradors as you can read here.)  Genes can also affect how the body stores fat or processes energy in cells.  That has a knock-on effect on obesity but (contrary to the expectations of those who first started to study obesity) that effect seems less important than the effect on appetite.

Studying obesity has improved our understanding of the fundamental biology of energy balance in the body.  It’s also identified real and potential drug targets.

For instance, secretion of a hormone from fat called Leptin is increased in obesity.  It acts on receptors in the hypothalamus to reduce appetite.  In normal circumstances, Leptin therefore acts to ‘turn down’ background hunger when there is plenty of reserve energy stored as fat in the body.  Human patients who are born without leptin become massively obese in early childhood but that can be reversed by treatment with leptin injections.

There are links to two good reviews about human obesity genetics on the links page.  You  can also hear GOdogs collaborating scientist Prof Farooqi speak about her work on obesity genetics on BBC Radio 4’s ‘The Life Scientific’ for a great introduction to the field.

What is Known about the Genetics of Obesity in Dogs?

Prior to GOdogs, a few small candidate gene studies comparing dogs to several other canid species have sought sequence variants in the candidate genes MC3R, MC4R, INSIG2 and FTO.  In red foxes, an association with measures of fat deposition was identified for single nucleotide variants (SNPs) in FTO, MC3R and INSIG2.

GOdogs have made further progress which you can read about on our website here.