I am a scientist specialized in genetics and metabolism.


Extreme diet and intensive exercise may be the best way to lose weight... and regain it afterwards.

In 10 seconds? Need to lose weight? Then you better avoid any miracle diets or intensive exercise programs that claim you will lose a lot in a jiffy, or you just may end up exhausted, hungrier and heavier than before.

Don’t believe it? Increasing energy expenditure and decreasing energy intake are today’s main approaches for losing weight, but when done in excess they cause a negative energy balance (too little intake, too much expenditure) that leads to a metabolic adaptation, by slowing down the resting metabolic rate and generating hunger, thus increasing food intake.

How can exercise lower resting metabolic rates? To avoid excessive energy expenditure and maintain energetic balance during high physical activity, the body lowers the basal metabolic rate, decreasing energy expenditure in several physiological tasks, while upregulating energy intake.

So am I doomed to regain the weight I lose? Well, it depends on the magnitude of the energy deficit that you suffered while loosing weight. For instance, participants of the reality show The Biggest Loser, a weight loss competition with significantly decreased energy intake and increased exercise, lost around 60 kg in a short time, but regained 60% of that weight after 6 years. Their resting metabolic rate was 20% lower after the competition, and it stayed low after 6 years, showing long-term metabolic adaptation. On the other hand, patients who lost weight after gastric bypass surgery had no detectable metabolic adaptation after 1 year, despite continued weight loss.

The bottom line is that you can not hurry nature, and that if you spent a lot of time gaining that weight, you will probably need some time to lose it too.


Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans.

Abstract: Current obesity prevention strategies recommend increasing daily physical activity, assuming that increased activity will lead to corresponding increases in total energy expenditure and prevent or reverse energy imbalance and weight gain [1-3]. Such Additive total energy expenditure models are supported by exercise intervention and accelerometry studies reporting positive correlations between physical activity and total energy expenditure [4] but are challenged by ecological studies in humans and other species showing that more active populations do not have higher total energy expenditure [5-8]. Here we tested a Constrained total energy expenditure model, in which total energy expenditure increases with physical activity at low activity levels but plateaus at higher activity levels as the body adapts to maintain total energy expenditure within a narrow range. We compared total energy expenditure, measured using doubly labeled water, against physical activity, measured using accelerometry, for a large (n = 332) sample of adults living in five populations [9]. After adjusting for body size and composition, total energy expenditure was positively correlated with physical activity, but the relationship was markedly stronger over the lower range of physical activity. For subjects in the upper range of physical activity, total energy expenditure plateaued, supporting a Constrained total energy expenditure model. Body fat percentage and activity intensity appear to modulate the metabolic response to physical activity. Models of energy balance employed in public health [1-3] should be revised to better reflect the constrained nature of total energy expenditure and the complex effects of physical activity on metabolic physiology.

Pub.: 03 Feb '16, Pinned: 11 May '17

Effect of calorie restriction on energy expenditure in overweight and obese adult women.

Abstract: Energy expenditure (EE) may decrease in subjects on hypocaloric diets, in amounts that exceed body mass loss, favoring weight regain.To verify if a short-term caloric restriction lowers Resting Energy Expenditure (REE) and Total Energy Expenditure (TEE) more than predicted by changes in body composition, and if this reduction of EE is related with compliance to the diet.Twenty-two women aged 23-44 years with a body mass index (BMI) of 25-32 kg/m2, underwent a three-month calorie restriction treatment (20 kcal/kg initial weight) and were encouraged to increase their physical activity. At the beginning and end of the intervention, body composition (DEXA), REE, Physical Activity Energy Expenditure (PAEE) and TEE were assessed, through a combination of indirect calorimetry and actigraphy. Participants, who lost more or equal than 5% of their initial weight were considered compliant with the diet.In the compliant group, REE decreased, when expressed in absolute numbers or when adjusted by fat free mass (FFM) [-164 ± 168 kcal/day (10,6%) and -4,3 ± 4,6 kcal/kg FFM (10,5%)]. This decline was significantly greater than that observed in the non-compliant group [-6,2 ± 1.42 Kcal/day (0.16%) and -0,5 ± 3,4/Kg FFM (0.96%)]. FFM did not change in any of the two groups. At baseline, there was a significant correlation between FFM and REE (r = 0, 56 p < 0,05), which was lost at the end of the intervention.Compliant women showed a significant reduction in both absolute and adjusted REE, which together with the loss of correlation between REE and FFM at the end of the intervention suggests a metabolic adaptation.

Pub.: 05 Jun '15, Pinned: 11 May '17

Imposed rate and extent of weight loss in obese men and adaptive changes in resting and total energy expenditure.

Abstract: Weight loss (WL) is associated with a decrease in total and resting energy expenditure (EE). We aimed to investigate whether (1) diets with different rate and extent of WL determined different changes in total and resting EE and if (2) they influenced the level of adaptive thermogenesis, defined as the decline in total or resting EE not accounted by changes in body composition.Three groups of six, obese men participated in a total fast for 6 days to achieve a 5% WL and a very low calorie (VLCD, 2.5 MJ/day) for 3 weeks or a low calorie (LCD, 5.2 MJ/day) diet for 6 weeks to achieve a 10% WL. A four-component model was used to measure body composition. Indirect calorimetry was used to measure resting EE. Total EE was measured by doubly labelled water (VLCD, LCD) and 24-hour whole-body calorimetry (fasting).VLCD and LCD showed a similar degree of metabolic adaptation for total EE (VLCD = -6.2%; LCD = -6.8%). Metabolic adaptation for resting EE was greater in the LCD (-0.4 MJ/day, -5.3%) compared to the VLCD (-0.1 MJ/day, -1.4%) group. Resting EE did not decrease after short-term fasting and no evidence of adaptive thermogenesis (+0.4 MJ/day) was found after 5% WL. The rate of WL was inversely associated with changes in resting EE (n = 30, r = 0.-42, p=0.01).The rate of WL did not appear to influence the decline in total EE in obese men after 10% WL. Approximately 6% of this decline in total EE was explained by mechanisms of adaptive thermogenesis.

Pub.: 25 Apr '15, Pinned: 11 May '17

The adaptive metabolic response to exercise-induced weight loss influences both energy expenditure and energy intake.

Abstract: A decline in resting energy expenditure (REE) beyond that predicted from changes in body composition has been noted following dietary-induced weight loss. However, it is unknown whether a compensatory downregulation in REE also accompanies exercise (EX)-induced weight loss, or whether this adaptive metabolic response influences energy intake (EI).Thirty overweight and obese women (body mass index (BMI)=30.6±3.6 kg/m(2)) completed 12 weeks of supervised aerobic EX. Body composition, metabolism, EI and metabolic-related hormones were measured at baseline, week 6 and post intervention. The metabolic adaptation (MA), that is, difference between predicted and measured REE was also calculated post intervention (MApost), with REE predicted using a regression equation generated in an independent sample of 66 overweight and obese women (BMI=31.0±3.9 kg/m(2)).Although mean predicted and measured REE did not differ post intervention, 43% of participants experienced a greater-than-expected decline in REE (-102.9±77.5 kcal per day). MApost was associated with the change in leptin (r=0.47; P=0.04), and the change in resting fat (r=0.52; P=0.01) and carbohydrate oxidation (r=-0.44; P=0.02). Furthermore, MApost was also associated with the change in EI following EX (r=-0.44; P=0.01).Marked variability existed in the adaptive metabolic response to EX. Importantly, those who experienced a downregulation in REE also experienced an upregulation in EI, indicating that the adaptive metabolic response to EX influences both physiological and behavioural components of energy balance.

Pub.: 09 Jan '14, Pinned: 11 May '17

PPAR-α as a key nutritional and environmental sensor for metabolic adaptation.

Abstract: Peroxisome proliferator-activated receptors (PPARs) are transcription factors that belong to the superfamily of nuclear hormone receptors and regulate the expression of several genes involved in metabolic processes that are potentially linked to the development of some diseases such as hyperlipidemia, diabetes, and obesity. One type of PPAR, PPAR-α, is a transcription factor that regulates the metabolism of lipids, carbohydrates, and amino acids and is activated by ligands such as polyunsaturated fatty acids and drugs used to treat dyslipidemias. There is evidence that genetic variants within the PPARα gene have been associated with a risk of the development of dyslipidemia and cardiovascular disease by influencing fasting and postprandial lipid concentrations; the gene variants have also been associated with an acceleration of the progression of type 2 diabetes. The interactions between genetic PPARα variants and the response to dietary factors will help to identify individuals or populations who can benefit from specific dietary recommendations. Interestingly, certain nutritional conditions, such as the prolonged consumption of a protein-restricted diet, can produce long-lasting effects on PPARα gene expression through modifications in the methylation of a specific locus surrounding the PPARα gene. Thus, this review underlines our current knowledge about the important role of PPAR-α as a mediator of the metabolic response to nutritional and environmental factors.

Pub.: 17 Jul '13, Pinned: 11 May '17