Genes & Weight

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Differences in your genes can influence how likely you are to be overweight. For example, genes can influence things like your appetite and how many calories you burn.  Variations in your genes also influence your weight by affecting how your body responds to exercise and to different types of nutrients like proteins, carbs and fats. The good news is that, by testing your DNA, you can find out what diet and exercise program might make it easier for you to lose weight.  Check out our review of genetics if you want a refresher.   Here are some examples of gene variations that can influence your weight based on your diet and exercise.

FTO Gene 

The FTO gene can have a significant influence on weight. The exact function of the FTO gene is unknown, but it appears to influence our appetite.

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Protein

 At one location in the FTO gene people can have AA, AT or TT variations.  In general, those who are AA or AT are more likely to be overweight than those who are TT.  What’s interesting is that people with AA or AT who eat a high protein diet are more likely to lose weight than those who eat a lower protein diet.[1]  This is true whether they eat a high or low fat diet. Some research has found that AA or AT people tend to normally have a higher appetite which is suppressed when they eat higher amounts of protein.[2]

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Exercise

Another set of variations in the FTO gene affect how a person responds to exercise.  In this case If you are AA or AT then being physically active, especially through aerobic activity, will be critical for helping you achieve a healthy weight.[3]  If you are TT then exercise, although important for maintaining your health, is less likely to impact your weight.   ]How does exercise help AA or AT individuals?

PPARG gene

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The PPARG gene appears to influence our weight and is sensitive to the type of diet that we eat.  PPARG affects how our body stores and breaks down the fats that we eat.[7] At one spot in the PPARG gene people can have GG, GC, or CC variations.  People who are GG or GC at a particular location in the PPARG gene are less likely to be overweight if they eat a “Mediterranean” style diet.[8]  Mediterranean style diets are high in a particular type of fat (MUFA) which is found in foods like olive oil and nuts. CC people, on the other hand, do better on a diet that is low in all fats. [9]   Individuals with any of the three variants tend to be lower weight if they follow a diet that is low in saturated fats.[10]  Saturated fats are found in higher levels in fatty meats and animal products such as butter and cheese.

 Plin1 gene

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People with AA or AG variations in the Plin1 gene sometimes find it more difficult to lose weight even when they are on a low calorie diet.[11]   What’s interesting is, that it becomes easier for them to lose weight if they eat a diet high in complex carbs like fruit, vegetables and whole grains.  [12],[13]  Weight loss is more difficult if they eat a diet low in complex carbs.  Not surprisingly, eating lots of simple carbs, on the other hand, like donuts and white bread doesn’t  help these individuals lose weight.


[1] Zhang X, Qi Q, Zhang C, et al. FTO genotype and 2-year change in body composition and fat distribution in response to weight-loss diets: The POUNDS LOST trial. Diabetes 2012; 61:3005–3011. A study testing hypothesis-driven gene–diet interaction in randomized diet intervention trial.

[2] Huang T1, Qi Q, Li Y, Hu FB, Bray GA, Sacks FM, Williamson DA, Qi L. Am.  FTO genotype, dietary protein, and change in appetite: the Preventing Overweight Using Novel Dietary Strategies trial. J Clin Nutr. 2014 Mar 12

[3] Andreasen CH  et al. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes. 2008 Jan;57(1):95-101.

[4] Broom DR et al. Influence of resistance and aerobic exercise on hunger, circulating levels of acylated ghrelin, and peptide YY in healthy males. Am J Physiol Regul Integr Comp Physiol. 2009 Jan;296(1):R29-35.

[5] Karra E et al. A link between FTO, ghrelin, and impaired brain food-cue responsivity. J Clin Invest. 2013 Aug 1;123(8):3539-51.

[6] Andreasen CH  et al. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes. 2008 Jan;57(1):95-101.

[7] Razquin C et al. (2009) . “The Mediterranean diet protects against waist circumference enlargement in 12Ala carriers for the PPARgamma gene: 2 years’ follow-up of 774 subjects at high cardiovascular risk.” Br J Nutr 102(5):672-9

[8] Marta Garaulet, Caren E Smith, Teresa Hernández-González,1 Yu-Chi Lee, and Jose M. Ordovás.  PPARγ Pro12Ala interacts with fat intake for obesity and weight loss in a behavioural treatment based on the Mediterranean diet.   Mol Nutr Food Res. Dec 2011; 55(12): 1771–1779.

[9] Memisoglu A  et al, Interaction between a peroxisome proliferator-activated receptor gamma gene polymorphism and dietary fat intake in relation to body mass.  Hum Mol Genet.  2003 Nov 15;12(22):2923-9.

[10] Memisoglu A  et al, Interaction between a peroxisome proliferator-activated receptor gamma gene polymorphism and dietary fat intake in relation to body mass.  Hum Mol Genet.  2003 Nov 15;12(22):2923-9.

[11] Corella et al. Obese subjects carrying the 11482G>A polymorphism at the perilipin locus are resistant to weight loss after dietary energy restriction. J Clin Endocrinol Metab. 2005 Sep; 90(9):5121-6.

[12] Caren E. Smith et al. Perilipin Polymorphism Interacts with Dietary Carbohydrates to Modulate Anthropometric Traits in Hispanics of Caribbean Origin J Nutr. Oct 2008; 138(10): 1852–1858.

[13] Corella D et al. Perilipin gene variation determines higher susceptibility to insulin resistance in Asian women when consuming a high-saturated fat, low-carbohydrate diet. Diabetes Care.  2006 Jun;29(6):1313-9.

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Photo attributions:

Chicken:  Photo obtained with permission from Justin Taylor Bludgeoner86 on flickr 

Exercise:  Photo obtained with permission from Urban Woman Magazine via flickr

Olive oil & Olives:  Photo obtained with permission from the USDA via flickr

Fruits & Veggies: Photo obtained with permission from the USDA via flickr