Fig 1.
Body fat phenotypes are determined by the “genetic lottery of life” and socioenvironmental factors.
A complex interplay between random genetic and epigenetic factors and social and environmental factors determines human fatness. In restrictive environments, i.e., environments where high energy expenditure is required to obtain few calorie-poor foods, variation in body weight is low simply because a subchronic negative energy balance prevents obesity-prone individuals from putting on weight. Conversely, obesogenic environments are characterized by high availability of hyperpalatable foods, and minimal physical efforts are required to obtain the next calorie-dense meal. Such environments reveal (1) parts of the population that are genetically predisposed to obesity (obesity prone), (2) individuals that only put on a moderate amount of fat mass (intermediate), and (3) individuals who have inherited a genetic “advantage” that allows them to stay lean (obesity resistant).
Fig 2.
Homeostatic regulation of body weight.
This simplified model suggests that homeostatic mechanisms protect against weight perturbations in either direction. The adipose-derived hormone leptin plays a key role in maintaining the “lower intervention” point in response to caloric restriction. Conversely, an “unidentified factor of overfeeding” has been hypothesized to counteract the overfed state around the upper intervention point. For already well-described factors implicated in body weight regulation, see references [7,34]. EE, energy expenditure; EI, energy intake.
Fig 3.
Naturally occurring periods of overfeeding: Lessons learned.
Left: Body weight change over time due to a culturally determined overfeeding period, exemplified here by observations from the Massa of Northern Cameroon and their collective (Guru) fattening session amongst young males. Blue area highlights the overfeeding period. Adapted after [45]. Right: Holiday weight gain showing the pulsatile change in body weight around holiday season in the 21st century. The slope of the curve suggests an incomplete weight recovery before the onset of the next holiday [49].
Fig 4.
Possible origins of the unidentified factor of overfeeding.
The putative circulating factor of overfeeding could be produced by a number of tissues including muscle, bone, pancreatic, hepatic, and adipose tissue. This blood-borne molecule is released from the tissue and works directly on appetite circuits within the central nervous system and/or indirectly by initially interacting with other peripheral organs. Its suggested chemical characteristics and previously excluded factors are mentioned in the box inserts.