To maintain a healthy body weight, you need to match food intake to energy expenditure, but you also need to be physically active and metabolically flexible!

Sedentary behavior is a risk factor for metabolic disease.

Contemporary societies have largely engineered physical activity out of daily life to the point that physical inactivity is now the 2^nd leading cause of death in the U.S. and the 4^th worldwide. This represents about 5.3 million deaths per year, which is equivalent to the 5 million deaths attributed to tobacco usage. This latter statistic has led to a media campaign targeting the catch phrase “Sitting is the new smoking!”. Indeed, it has become evident that sedentary behaviors (e.g. sitting) play an independent and critical role in the development of metabolic diseases, such as obesity and type 2 diabetes.

Maintaining body weight requires that energy intake matches energy expenditure.

To maintain a stable body weight, energy intake needs to be equal to energy expenditure. One explanation for the association between time spent sedentary and unhealthy weight is that a sedentary person is unable to decrease food intake enough to match low levels of energy expenditure. As a result, calorie intake exceeds the amount of energy expended, and these calories will be stored leading to weight gain. When a person gains weight, the body needs to burn more energy to move, which leads to an increase in energy expenditure even if the person remains sedentary. This phenomenon will occur until a new steady state is reached. In other words, until energy intake matches energy expenditure but at higher levels because the person is now heavier. Regulation of energy balance (i.e. result between energy intake and expenditure) is the cornerstone of body weight regulation, and most likely plays key role in the relationship observed between sedentary behaviors and unhealthy weight. In support of this, we recently showed that increased sedentary behaviors in the days following a period of overfeeding, like we often have during holidays, may be one mechanism that contributes to weight gain over the long term, specifically fat mass gain (Creasy et al. Obesity 2018).

Maintaining body weight requires that the amount of carbohydrate, fat, and protein you ingest matches the amount burned.

Our diet is composed of fat, carbohydrate and protein that are used by the body as fuel to provide energy. To maintain a stable body weight, it is necessary that the amount of fat, protein and carbohydrate burned by the body correspond to the amount ingested. If this does not happen calories will be stored as fat in the body, leading to body weight gain. A healthy person is able to adapt the use of fat, protein and carbohydrate to changes in their availability. Most of the time availability is driven by changes in dietary intake. This phenomenon is defined as “metabolic flexibility”. Persons with obesity or type 2 diabetes are unable to adjust substrates use to changes in their availability; they are “metabolically inflexible”. This means that when faced with a metabolic challenge such as Thanksgiving dinner, a metabolically inflexible person will not be able to cope with this sudden large amount of food and will store more than a person who is metabolically flexible. Of course, this is not observed after a single meal but over periods of overeating such as weekends, special occasions, and holidays. A focus of our research is to determine how metabolic flexibility is regulated and determine why some people are metabolically flexible while others are metabolically inflexible.

Do sedentary behaviors trigger metabolic inflexibility?

Genetics, sex, ethnicity and other individual factors most certainly play a role in determining metabolic flexibility. However, factors that can be modified such as exercise habits and daily sedentary behaviors appear to be key determinants of metabolic flexibility. Even if lifestyle changes can be challenging to implement and sustain, daily physical activity is one of the most variable traits among humans! By combining several studies in which we asked participants to either increase or decrease their physical activity, we showed that habitual levels of physical activity predict metabolic flexibility (Bergouignan et al. JAP 2011). Even in persons who are overweight and obese, increasing physical activity over 2 months improves metabolic flexibility (Lefai et al. Int J Obes 2017). Taking these studies and others into account, we hypothesized in our most recent review article that sedentary behaviors trigger a metabolically inflexible state (Rynders et al. J Physiol 2017). In other words, Kate who is an office worker and spends 8 hours per day at her desk will be less able to handle a period of overeating than Mary who delivers mail by foot 5 days a week. We focused on overeating in our review, but there are other situations that can modulate metabolic flexibility such as exercise, pregnancy, night shift work, sleep duration, long stays at the hospital, etc. In regards to the latter example, we recently demonstrated in healthy men who were on bedrest for 21 days that metabolic inflexibility is a direct consequence of physical inactivity (Rudwill et al. J Clin Endo Metab 2018). Bed rest is an extreme example of inactivity, so additional studies are warranted to confirm this finding at levels of inactivity closer to what we observe in the general population.

Why is all of this important?

Although additional studies are needed to demonstrate the direct effect of sedentary behaviors, we are accumulating data to show that sedentary behaviors are a key player in the development of metabolic inflexibility, and thus metabolic diseases. We believe understanding the relationships between sedentary behaviors and metabolic flexibility will change how we manage and treat obesity. For example, in the context of weight loss and long-term weight maintenance we should be thinking about physical activity, not only as a tool to expend energy, but also as a way to reset the system and allow the body to face daily changes in food intake and other life events that serve as metabolic stressors.

 References

* Co-first authors; #Co-last authors

Creasy SA, Rynders CA, Bergouignan A, Kealey EH, Bessesen DH. Free-living responses in energy balance to short-term overfeeding in adults differing in propensity for obesity. Obesity (Silver Spring). 2018 Apr;26(4):696-702.

Lefai E*, Blanc S*, Antoun E, Momken I, Chery I, Zahariev A, Gabert L, Bergouignan A^#, Simon C^#. Exercise training improves fat metabolism independent of total energy expenditure in sedentary overweight men, but does not restore lean metabolic phenotype. Int J Obes (Lond). 2017 Jul 3.

Rudwill F*, O’Gorman D*, Lefai E, Chery I, Zahariev A, Normand S, Pagano AF, Chopard A, Damiot A, Laurens C, Hodson L, Canet-Soulas E, Heer M, Frings Meuthen P, Buehlmeier J, Baecker N, Meiller L, Gauquelin-Koch G, Blanc S^#, Simon C^#, Bergouignan A^#. Metabolic inflexibility is an early marker of bed-rest induced glucose intolerance even when fat mass is stable. J Clin Endocrinol Metab.

Rynders CA, Blanc S, DeJong N, Bessesen DH, Bergouignan A. Sedentary behaviors as a key determinant of metabolic flexibility. J Physiol, 2017 May 24.

Authors

Audrey Bergouignan leads an International Associated Lab (LIA) between the French Research Center for Scientific Research (CNRS) Institut Pluridisciplinaire Hubert Curien (IPHC) and the University of Colorado Division of Endocrinology and Anschutz Health & Wellness Center that aims at addressing the health impact of the global transition of physical activity. She is an integrative physiologist whose research focuses on the study of energy balance and metabolic flexibility, and their regulation by environmental factors, i.e. physical activity, sedentary behaviors and diet. A special focus of her research is to delineate the mechanisms by which sedentary behaviors contribute to the development and progression of metabolic diseases.

Corey Rynders is an Assistant Professor in the Division of Geriatric Medicine and a member of the IMAGE (Investigations in Metabolism, Aging, Gender and Exercise) Research Group at the University of Colorado – Anschutz Medical Campus. His current research is focused on understanding how manipulating energy balance and the timing of behaviors (exercise, dietary intake, and sleep) alters metabolic flexibility. He is also working on a project to understand the role of exercise and sedentary behaviors in people who have lost weight to determine the extent these factors are involved in promoting or protecting against weight regain.