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In The Obese, Metabolic Adaptations After Weight Loss Lead To The
Regaining Of The Shed Pounds

These changes cause the body’s metabolism to have a preference for carbohydrates use

(June 28, 2004) --  Bethesda, MD - After months of torturous dieting, there is nothing more frustrating than to find that the lost weight has returned. Many dieters are shocked to see they have returned to their original weight despite modifications in exercise and eating habits.  Now a new animal study reveals that when loss occurs, metabolic adaptations occur that mandate a return of the undesired pounds. 

Background

These findings address a key question of whether regaining loss weight due to dieting is caused by metabolic or behavioral changes.  The common belief is that the metabolic state after weight loss promotes weight regain. However, data germane to this supposition has been controversial and equivocal. 

The failure to reach definitive conclusions in between these studies is linked to the way metabolic mass is estimated, the selection of research subjects, and the methods of weight loss and weight maintenance.  Human studies are impractical, because there is no way to identify individuals predisposed to the development of obesity.  Even if such identification was possible, it would be difficult to follow them throughout the protracted course of the development, treatment, and recurrence of their obese state. 

Rats offer a better opportunity to address this issue. The ability to select obesity-prone rats, coupled with the shorter lifespan of the test animals and a better ability to control environmental conditions, offers researchers the opportunity to examine the metabolic state of an obese rat.

A New Study

This is the framework of a study performed through an assessment of indirect calorimetry, the balance of energy and fuel utilization in these obesity-prone rats throughout five stages of obesity development, treatment, and recurrence.  Those stages are (1) pre-obesity; (2) established obesity; (3) weight-reduced; (4) weight-reduced after a period of weight maintenance; and (5) weight-reduced after a period of regaining the lost weight.

The goal of the study was to collect data that offered insight to the metabolic adjustments that occur in response to weight loss and maintenance that make successful weight maintenance a challenging prospect. 

The authors of the study, “Metabolic Adjustments with the Development, Treatment, and Recurrence of Obesity in Obesity-Prone Rats,” are Paul S. MacLean, Janine A. Higgins, Ginger C. Johnson, Brooke K. Fleming-Elder, and James O. Hill, from the University of Colorado Health Sciences Center, Denver, CO; and John C. Peters, from the Procter and Gamble Company. Their findings appear in the online edition of the American Journal of Physiology – Regulatory, Integrative and Comparative Physiology. The journal is one of 14 published each month by the American Physiological Society (www.the-aps.org).

Methodology

The study design consisted of placing 13 obesity-prone rats on a high fat diet for a period of 16 weeks to promote the development of obesity. These obese rats were examined metabolically and represent a group of rats with established obesity (established obesity, EO). These rats were then placed on a low fat, energy restricted diet that would produce a 10-15 percent loss in body weight during two weeks of caloric restriction and again underwent metabolic examination (weight loss, WL). Weight loss was targeted to achieve a 10-15 percent loss in body weight that would be reflective of target adjustments in human weight loss programs. To achieve this objective, weight loss was induced by limiting calories to approximately 60 percent of energy expenditure, with a daily monitoring and adjustment of food intake throughout the 14-day period to ensure a negative energy balance.

Six of the 13 calorically restricted rats were then assigned to a weight maintained group (WM), while the other seven were randomly assigned to a weight regain group (WR). The assignment of the rats to WM and WR groups was based upon having the two groups stratified by body weight and total weight loss. WM rats were subsequently maintained at this reduced weight with restricted energy intake for eight weeks before again being examined, while WR rats were allowed to regain weight with at-will access to a low fat diet for eight weeks before being examined. Three other separate groups were employed as controls. One group of seven rats was examined immediately after the screening process (pre-obesity, PO). Another group of seven rats was fed a high fat diet for 16 weeks and then examined after being switched to a low fat diet for 10 weeks to represent an age-matched diet-matched control (low fat diet control, LFC). The last group of eight rats was fed a high fat diet for 16 weeks, as with the other groups, but examined after being continued with this regimen for another 10 weeks (high fat diet control, HFC). Body weight was monitored regularly throughout the entire study. Energy balance, fuel utilization and body composition were determined at specified time points corresponding to the various stages of the development, treatment, and recurrence of obesity.

The goal of the research was to determine if there is a metabolic propensity to regain weight after a period of significant weight loss.  Accordingly, 24 hour energy expenditure (EE), sleeping metabolic rate (SMR), and non-protein respiratory quotient (NPRQ) were obtained by indirect calorimetry with urinary nitrogen analysis and normalized to fat mass (FM) and fat free mass (FFM) acquired by dual energy x-ray absorptiometry.

Results

This study provides insight as to how the metabolic state of an obesity-prone rat changes from the pre-obese state to the obese state. 

The first conclusion reached from the data is that the transition from the pre-obese to the obese state is accompanied by an increase in metabolic rate and metabolic efficiency but little alteration in the utilization of fuels outside of that explained by the variation in the type and amount of diet consumed. 

The obesity-prone rats in the present study do reflect obesity-prone humans in a number of aspects.  Accordingly, when compared to obesity-resistant counterparts, obesity-prone rats: (1) eat more; (2) have a lower 24-hr energy expenditure under conditions leading to obesity ; and (3) have an elevated 24 hour NPRQ on both low and high fat diets.

The researchers observed that a 14 percent loss in body weight induced by calorie restriction is accompanied by a 17 percent reduction in EE and 18 percent in SMR, and a suppressed NPRQ. Both EE and SMR declined to a greater extent than was expected from the combination of loss of body mass and reduction in energy intake, suggesting an increase in metabolic efficiency. NPRQ remained lower after the adjustment of energy balance and carbohydrate (CHO) intake, suggesting a preference for lipid use. Thus, weight loss from calorie restriction is accompanied by an increase in metabolic efficiency and a preference for the use of lipids as opposed to CHO.

No change was found from the weight-reduced state in energy expenditure or sleep metabolic rate when the rats were maintained at a constant, reduced body weight for eight subsequent weeks, suggesting that metabolic efficiency was still higher after a prolonged period of weight maintenance.  The researchers did determine that carbohydrate disappearance was proportionally higher. Thus, the second major conclusion is that continued maintenance of a reduced body weight was accompanied by an elevation in metabolic efficiency and shift in fuel utilization such that there was a preference for carbohydrate use more so than what was expected from the diet consumed, or in other words, the body wants carbs that lead to weight gain.

Conclusions

The data suggests that weight loss in obese, obesity-prone rats, induced by caloric restriction, is accompanied by metabolic adaptations that predispose one to regain the lost weight. In rats that are losing weight, this is exhibited by a significant reduction in metabolic rate, measured as both 24-hour energy expenditure and sleeping metabolic rate, both independent of metabolic mass and energy intake. This adaptation persists after eight weeks of intake-regulated weight maintenance, but is no longer present with eight subsequent weeks of feeding at-will where rats are regaining lost weight. While rats that are regaining weight may have a shift in appetite that would contribute to their high rate of weight regain, the drive to increase food intake remains the most critical factor in the predisposition to regain lost weight. This adjustment clearly weighs more on the energy balance equation than the metabolic adjustment on energy expenditure observed in this or any other study.

Additionally, the effect that energy intake, or more particularly, carbohydrate intake, has on respiratory quotient [dividing the amount of CO2 produced (VCO2) by the amount of oxygen uptake (VO2)]. RQ is much more dramatic than the metabolic adjustment observed from weight reduction. This drive to increase food intake likely involves environmental stimuli (diet composition, food palatability, physical activity) influencing motivational and metabolic components of a genetically determined set of central systems.

While the data suggest that these metabolic adaptations might hinder successful weight maintenance, it should not imply that successful weight maintenance is unachievable. Even with the increased intake of carbohydrates, regular physical exercise may be the key factor that counteracts these metabolic adaptations to weight loss.

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Source: Online edition of the American Journal of Physiology – Regulatory, Integrative and Comparative Physiology. The  journal is one of 14 published each month by the American Physiological Society (www.the-aps.org).

The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.

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Editor’s Note: A copy of the research article is available in pdf format to the press. Members of the press are invited to obtain a pdf copy of the study and to interview members of the research team. To do so, please contact Donna Krupa at (301) 634-7209 (direct dial), (703) 967-2751 (cell) or dkrupa@the-aps.org.