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Eric Jéquier

Bio: Eric Jéquier is an academic researcher from University of Lausanne. The author has contributed to research in topics: Carbohydrate metabolism & Insulin. The author has an hindex of 57, co-authored 168 publications receiving 26634 citations. Previous affiliations of Eric Jéquier include Bayer HealthCare Pharmaceuticals & University Hospital of Lausanne.


Papers
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Journal ArticleDOI
TL;DR: In humans, the leptin signaling system appears to be mainly involved in maintenance of adequate energy stores for survival during periods of energy deficit, and its role in the etiology of human obesity is only demonstrated in the very rare situations of absence of the leptin signal.
Abstract: A chronic minor imbalance between energy intake and energy expenditure may lead to obesity. Both lean and obese subjects eventually reach energy balance and their body weight regulation implies that the adipose tissue mass is "sensed", leading to appropriate responses of energy intake and energy expenditure. The cloning of the ob gene and the identification of its encoded protein, leptin, have provided a system signaling the amount of adipose energy stores to the brain. Leptin, a hormone secreted by fat cells, acts in rodents via hypothalamic receptors to inhibit feeding and increase thermogenesis. A feedback regulatory loop with three distinct steps has been identified: (1) a sensor (leptin production by adipose cells) monitors the size of the adipose tissue mass; (2) hypothalamic centers receive and integrate the intensity of the leptin signal through leptin receptors (LRb); (3) effector systems, including the sympathetic nervous system, control the two main determinants of energy balance-energy intake and energy expenditure. While this feedback regulatory loop is well established in rodents, there are many unsolved questions about its applicability to body weight regulation in humans. The rate of leptin production is related to adiposity, but a large portion of the interindividual variability in plasma leptin concentration is independent of body fatness. Gender is an important factor determining plasma leptin, with women having markedly higher leptin concentrations than men for any given degree of fat mass. The ob mRNA expression is also upregulated by glucocorticoids, whereas stimulation of the sympathetic nervous system results in its inhibition. Furthermore, leptin is not a satiety factor in humans because changes in food intake do not induce short-term increases in plasma leptin levels. After its binding to LRb in the hypothalamus, leptin stimulates a specific signaling cascade that results in the inhibition of several orexigenic neuropeptides, while stimulating several anorexigenic peptides. The orexigenic neuropeptides that are downregulated by leptin are NPY (neuropeptide Y), MCH (melanin-concentrating hormone), orexins, and AGRP (agouti-related peptide). The anorexigenic neuropeptides that are upregulated by leptin are alpha-MSH (alpha-melanocyte-stimulating hormone), which acts on MC4R (melanocortin-4 receptor); CART (cocaine and amphetamine-regulated transcript); and CRH (corticotropin-releasing-hormone). Obese humans have high plasma leptin concentrations related to the size of adipose tissue, but this elevated leptin signal does not induce the expected responses (i.e., a reduction in food intake and an increase in energy expenditure). This suggests that obese humans are resistant to the effects of endogenous leptin. This resistance is also shown by the lack of effect of exogenous leptin administration to induce weight loss in obese patients. The mechanisms that may account for leptin resistance in human obesity include a limitation of the blood-brain-barrier transport system for leptin and an inhibition of the leptin signaling pathways in leptin-responsive hypothalamic neurons. During periods of energy deficit, the fall in leptin plasma levels exceeds the rate at which fat stores are decreased. Reduction of the leptin signal induces several neuroendocrine responses that tend to limit weight loss, such as hunger, food-seeking behavior, and suppression of plasma thyroid hormone levels. Conversely, it is unlikely that leptin has evolved to prevent obesity when plenty of palatable foods are available because the elevated plasma leptin levels resulting from the increased adipose tissue mass do not prevent the development of obesity. In conclusion, in humans, the leptin signaling system appears to be mainly involved in maintenance of adequate energy stores for survival during periods of energy deficit. Its role in the etiology of human obesity is only demonstrated in the very rare situations of absence of the leptin signal (mutations of the leptin gene or of the leptin receptor gene), which produces an internal perception of starvation and results in a chronic stimulation of excessive food intake.

761 citations

Journal ArticleDOI
TL;DR: To further validate the doubly labeled water method for measurement of CO2 production and energy expenditure in humans, it is compared with near-continuous respiratory gas exchange in nine healthy young adult males.
Abstract: To further validate the doubly labeled water method for measurement of CO2 production and energy expenditure in humans, we compared it with near-continuous respiratory gas exchange in nine healthy young adult males. Subjects were housed in a respiratory chamber for 4 days. Each received 2H2(18)O at either a low (n = 6) or a moderate (n = 3) isotope dose. Low and moderate doses produced initial 2H enrichments of 5 and 10 X 10(-3) atom percent excess, respectively, and initial 18O enrichments of 2 and 2.5 X 10(-2) atom percent excess, respectively. Total body water was calculated from isotope dilution in saliva collected at 4 and 5 h after the dose. CO2 production was calculated by the two-point method using the isotopic enrichments of urines collected just before each subject entered and left the chamber. Isotope enrichments relative to predose samples were measured by isotope ratio mass spectrometry. At low isotope dose, doubly labeled water overestimated average daily energy expenditure by 8 +/- 9% (SD) (range -7 to 22%). At moderate dose the difference was reduced to +4 +/- 5% (range 0-9%). The isotope elimination curves for 2H and 18O from serial urines collected from one of the subjects showed expected diurnal variations but were otherwise quite smooth. The overestimate may be due to approximations in the corrections for isotope fractionation and isotope dilution. An alternative approach to the corrections is presented that reduces the overestimate to 1%.

689 citations

Journal ArticleDOI
TL;DR: A comparison of direct and indirect methods for Calorimetry with respect to the 2H2180 technology shows that direct methods are superior to indirect methods in terms of accuracy and efficiency.
Abstract: DIRECT AND INDIRECT CALORIMETRY .. . . . .... . . . . ... . . ..... . . . ..... . ..... . ..... . . ..... . 1 87 Introduction 1 87 Heat Balance Equation ...... 188 Direct Calorimetry . . . . ...... . ....... ...... . . . .. . . . . . . . . . . . . . . . ... . . . .. ..... .... 1 89 Indirect Calorimetry..... . . . . . . . . . . . . . . . . . .. . . . ..... . ... . . . . . . . . . . ... . . . . . . . . . . . . . . . . . ... . . . ...... 190 Indirect Calormietry with a Respiration Chamber 192 FUEL UTILIZATION IN MAN . . . ..... . . . . ..... . ....... .... . ....... ..... . ...... ... . . 193 Theoretical Limitations ..... . . . .. ..... ... . . . ..... . . . .... . . .... . . . . . .... . . .... . ..... .... 195 Physiological Considerations. .. . ........ . . . .... . ..... . . ..... . . .. . . . . .... . ..... . .... . . ...... .... 196 Stoichiometry .. . . ... . . . . . ... . . ........ . ... ...... ..... . . ..... ..... ......... . . ... . .... . . 200 NONCALORIMETRIC METHODS WITH REFERENCE TO THE 2H2180 TECHNIQUE . . . . . . . . . . .. . . . . ..... . . ..... . . ..... . . ... . . . ... . . . .... . .. . . . . ... . . ... . . . . ... . . 203

506 citations

Journal ArticleDOI
TL;DR: The aim of this review is to describe the physiology of water balance and consequently to highlight the new recommendations with regard to water requirements.
Abstract: How much water we really need depends on water functions and the mechanisms of daily water balance regulation. The aim of this review is to describe the physiology of water balance and consequently to highlight the new recommendations with regard to water requirements. Water has numerous roles in the human body. It acts as a building material; as a solvent, reaction medium and reactant; as a carrier for nutrients and waste products; in thermoregulation; and as a lubricant and shock absorber. The regulation of water balance is very precise, as a loss of 1% of body water is usually compensated within 24 h. Both water intake and water losses are controlled to reach water balance. Minute changes in plasma osmolarity are the main factors that trigger these homeostatic mechanisms. Healthy adults regulate water balance with precision, but young infants and elderly people are at greater risk of dehydration. Dehydration can affect consciousness and can induce speech incoherence, extremity weakness, hypotonia of ocular globes, orthostatic hypotension and tachycardia. Human water requirements are not based on a minimal intake because it might lead to a water deficit due to numerous factors that modify water needs (climate, physical activity, diet and so on). Water needs are based on experimentally derived intake levels that are expected to meet the nutritional adequacy of a healthy population. The regulation of water balance is essential for the maintenance of health and life. On an average, a sedentary adult should drink 1.5 l of water per day, as water is the only liquid nutrient that is really essential for body hydration.

494 citations


Cited by
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Journal ArticleDOI
06 May 2000-BMJ
TL;DR: The proposed cut off points, which are less arbitrary and more internationally based than current alternatives, should help to provide internationally comparable prevalence rates of overweight and obesity in children.
Abstract: Objective To develop an internationally acceptable definition of child overweight and obesity, specifying the measurement, the reference population, and the age and sex specific cut off points. Design International survey of six large nationally representative cross sectional growth studies. Setting Brazil, Great Britain, Hong Kong, the Netherlands, Singapore, and the United States. Subjects 97 876 males and 94 851 females from birth to 25 years of age. Main outcome measure Body mass index (weight/height 2 ). Results For each of the surveys, centile curves were drawn that at age 18 years passed through the widely used cut off points of 25 and 30 kg/m 2 for adult overweight and obesity. The resulting curves were averaged to provide age and sex specific cut off points from 2›18 years. Conclusions The proposed cut off points, which are less arbitrary and more internationally based than current alternatives, should help to provide internationally comparable prevalence rates of overweight and obesity in children.

14,792 citations

Journal ArticleDOI
TL;DR: It was agreed that there should not be an obligatory component, but that waist measurement would continue to be a useful preliminary screening tool, and a single set of cut points would be used for all components except waist circumference, for which further work is required.
Abstract: A cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus, which occur together more often than by chance alone, have become known as the metabolic syndrome. The risk factors include raised blood pressure, dyslipidemia (raised triglycerides and lowered high-density lipoprotein cholesterol), raised fasting glucose, and central obesity. Various diagnostic criteria have been proposed by different organizations over the past decade. Most recently, these have come from the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. The main difference concerns the measure for central obesity, with this being an obligatory component in the International Diabetes Federation definition, lower than in the American Heart Association/National Heart, Lung, and Blood Institute criteria, and ethnic specific. The present article represents the outcome of a meeting between several major organizations in an attempt to unify criteria. It was agreed that there should not be an obligatory component, but that waist measurement would continue to be a useful preliminary screening tool. Three abnormal findings out of 5 would qualify a person for the metabolic syndrome. A single set of cut points would be used for all components except waist circumference, for which further work is required. In the interim, national or regional cut points for waist circumference can be used.

11,737 citations

Journal ArticleDOI
TL;DR: The proportion of Asian people with a high risk of type 2 diabetes and cardiovascular disease is substantial at BMIs lower than the existing WHO cut-off point for overweight (> or =25 kg/m2), but available data do not necessarily indicate a clear BMI cut-offs point for all Asians for overweight or obesity.

9,536 citations

Journal Article
TL;DR: These definitions are offered as an interpretational framework for comparing studies that relate physical activity, exercise, and physical fitness to health.
Abstract: "Physical activity," "exercise," and "physical fitness" are terms that describe different concepts. However, they are often confused with one another, and the terms are sometimes used interchangeably. This paper proposes definitions to distinguish them. Physical activity is defined as any bodily movement produced by skeletal muscles that results in energy expenditure. The energy expenditure can be measured in kilocalories. Physical activity in daily life can be categorized into occupational, sports, conditioning, household, or other activities. Exercise is a subset of physical activity that is planned, structured, and repetitive and has as a final or an intermediate objective the improvement or maintenance of physical fitness. Physical fitness is a set of attributes that are either health- or skill-related. The degree to which people have these attributes can be measured with specific tests. These definitions are offered as an interpretational framework for comparing studies that relate physical activity, exercise, and physical fitness to health.

7,608 citations

Journal ArticleDOI
09 Oct 2002-JAMA
TL;DR: The increases in the prevalences of obesity and overweight previously observed continued in 1999-2000, and increases occurred for both men and women in all age groups and for non-Hispanic whites, non- Hispanic blacks, and Mexican Americans.
Abstract: ContextThe prevalence of obesity and overweight increased in the United States between 1978 and 1991. More recent reports have suggested continued increases but are based on self-reported data.ObjectiveTo examine trends and prevalences of overweight (body mass index [BMI] ≥25) and obesity (BMI ≥30), using measured height and weight data.Design, Setting, and ParticipantsSurvey of 4115 adult men and women conducted in 1999 and 2000 as part of the National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the US population.Main Outcome MeasureAge-adjusted prevalence of overweight, obesity, and extreme obesity compared with prior surveys, and sex-, age-, and race/ethnicity–specific estimates.ResultsThe age-adjusted prevalence of obesity was 30.5% in 1999-2000 compared with 22.9% in NHANES III (1988-1994; P<.001). The prevalence of overweight also increased during this period from 55.9% to 64.5% (P<.001). Extreme obesity (BMI ≥40) also increased significantly in the population, from 2.9% to 4.7% (P = .002). Although not all changes were statistically significant, increases occurred for both men and women in all age groups and for non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. Racial/ethnic groups did not differ significantly in the prevalence of obesity or overweight for men. Among women, obesity and overweight prevalences were highest among non-Hispanic black women. More than half of non-Hispanic black women aged 40 years or older were obese and more than 80% were overweight.ConclusionsThe increases in the prevalences of obesity and overweight previously observed continued in 1999-2000. The potential health benefits from reduction in overweight and obesity are of considerable public health importance.

6,523 citations