Individual Responses to Overeating

Just to follow up on the recent article that Bret Contreras and I wrote on genetic variation in responses to diet and training, here's a recent review article on the genetic differences in response to overfeeding. First, people vary widely in the amount of weight they gain when overfed a certain number of calories (this is partly due to genetic differences in the NEAT response to overfeeding, which I've talked about in my NEAT lectures...neat, huh?). Also, for a given amount of weight gain, people will vary in their susceptibility to the complications of weight gain, such as metabolic syndrome and heart disease. This paper discusses that one factor related to your susceptibility to disease with weight gain is your body's ability to expand subcutaneous (under the skin) fat tissue (SAT) in response to overfeeding (this is called the adipose expandability hypothesis). SAT has limits to how much it can expand, and you get a "spillover" into ectopic fat (fat surrounding organs and in your muscle). It's this ectopic fat that is mainly responsible for disease risk. People vary in how much SAT can expand, and thus vary in how much ectopic fat they deposit when overfeeding. This is why you can get leaner people with metabolic disorders, and overweight/obese people who are relatively metabolically healthy.

What have human experimental overfeeding studies taught us about adipose tissue expansion and susceptibility to obesity and metabolic complications?

Review article

Cuthbertson DJ, et al. Int J Obes (Lond). 2017.


Cuthbertson DJ1,2, Steele T1, Wilding JP1,2, Halford JC3, Harrold JA3, Hamer M4, Karpe F5.

Author information

  • 1Obesity and Endocrinology Research Group, University Hospital Aintree, UK.
  • 2Institute of Ageing and Chronic Disease, University of Liverpool.
  • 3Psychological Sciences, Eleanor Rathbone Building, University of Liverpool, Liverpool, UK.
  • 4National Centre for Sport & Exercise Medicine, Loughborough University.
  • 5Oxford Centre for Diabetes, Endocrinology & Metabolism.


Int J Obes (Lond). 2017 Jan 12. doi: 10.1038/ijo.2017.4. [Epub ahead of print]


Overfeeding experiments, in which we impose short-term positive energy balance, help unravel the cellular, physiological and behavioural adaptations to nutrient excess. These studies mimic longer-term mismatched energy expenditure and intake. There is considerable inter-individual heterogeneity in the magnitude of weight gain when exposed to similar relative caloric excess reflecting variable activation of compensatory adaptive mechanisms. Significantly, given similar relative weight gain, individuals may be protected from/predisposed to metabolic complications (insulin resistance, dyslipidaemia, hypertension), non-alcoholic fatty liver disease and cardiovascular disease. Similar mechanistic considerations underpinning the heterogeneity of overfeeding responses are pertinent in understanding emerging metabolic phenotypes e.g. metabolically unhealthy normal weight and metabolically healthy obesity. Intrinsic and extrinsic factors modulate individuals' overfeeding response: intrinsic factors include gender/hormonal status, genetic/ethnic background, baseline metabolic health and cardiorespiratory fitness; extrinsic factors include macronutrient (fat vs carbohydrate) content, fat/carbohydrate composition and overfeeding pattern. Subcutaneous adipose tissue (SAT) analysis, coupled with metabolic assessment, with overfeeding have revealed how SAT remodels to accommodate excess nutrients. SAT remodelling occurs either by hyperplasia (increased adipocyte number) or by hypertrophy (increased adipocyte size). Biological responses of SAT also govern the extent of ectopic (visceral/liver) triglyceride deposition. Body composition analysis by DEXA/MRI have determined the relative expansion of SAT (including abdominal/gluteofemoral SAT) versus ectopic fat with overfeeding. Such studies have contributed to the adipose expandability hypothesis whereby SAT has a finite capacity to expand (governed by intrinsic biological characteristics) and once capacity is exceeded ectopic triglyceride deposition occurs. The potential for SAT expandability confers protection from/predisposes to the adverse metabolic responses to over-feeding. The concept of a personal fat threshold suggests a large inter-individual variation in SAT capacity with ectopic depot expansion/metabolic decompensation once one's own threshold is exceeded. This review summarises insight gained from overfeeding studies regarding susceptibility to obesity and related complications with nutrient excess.

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