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Biomedical subjects

J Jacquet

Publications and source records attributed to J Jacquet.

At least 19 recordsLinked to original sources
PubMed2002

Pathways from weight fluctuations to metabolic diseases: focus on maladaptive thermogenesis during catch-up fat.

It has long been known that obesity is a high risk factor for cardiovascular diseases. In more recent years, the analysis of several large epidemiological databases has also revealed that, independently of excess weight, large fluctuations in body weight at some point earlier in life represent an independent risk factor for type 2 diabetes and hypertension-two major contributors to cardiovascular diseases. High cardiovascular morbidity and mortality have indeed been reported in men and women who in young adulthood experienced weight fluctuations (involving the recovery of body weight after weight loss due to disease, famine or voluntary slimming), or when weight fluctuations occurred much earlier in life and involved catch-up growth after fetal or neonatal growth retardation. This paper addresses the pathways from weight fluctuations to chronic metabolic diseases by focusing on the phenomenon of accelerated fat recovery (ie catch-up fat) after weight loss or growth retardation. Arguments are put forward that, during catch-up growth or weight recovery on our modern refined foods, the mechanisms of adaptive thermogenesis that regulate catch-up fat are pushed beyond the limits for which they were meant to operate and turn maladaptive. The consequences are enhanced susceptibilities towards skeletal muscle insulin resistance and overactive sympathetic activity, both of which are major contributors to the pathogenesis of chronic metabolic diseases. Since weight fluctuation earlier in life (independently of excess weight later in life) is an independent risk factor for metabolic diseases, the mechanisms by which body fat is acquired would seem to be at least as important as the consequences of excess fat per se in the pathogenesis of diabetes, hypertension and cardiovascular diseases.

Adipose Tissue↗
PubMed2001

An adipose-specific control of thermogenesis in body weight regulation.

Much of our understanding about 'adaptive thermogenesis' as a control system in mammalian weight regulation derives from studies of experimental starvation and overfeeding, and these have served to characterize its functional role as an 'attenuator' of energy imbalance. By applying a system-analysis approach in evaluating data on the energetics of starvation and refeeding, evidence is presented here in support of the hypothesis that there are in fact two distinct control systems underlying adaptive thermogenesis. In one of them, the efferent limb is primarily under the control of the sympathetic nervous system (SNS), whose functional state is dictated by overlapping or interacting signals arising from a variety of environmental stresses, including food deprivation, deficiency of essential nutrients, excess energy intake and exposure to cold or to infections; it is hence referred to as the non-specific control of thermogenesis, and is likely to occur primarily in organs/tissues with a high specific metabolic rate (eg liver, kidneys, brown fat). The other is independent of the functional state of the SNS and is dictated solely by signals arising from the state of depletion of the adipose tissue fat stores; it is hence referred to as the adipose-specific control of thermogenesis, and is postulated to occur primarily in the skeletal muscle. While suppression of this adipose-specific thermogenesis during both starvation and refeeding leads to energy conservation, the energy spared during refeeding is directed specifically at the replenishment of the fat stores, so that it functions as an 'accelerator' of fat recovery. These two distinct control systems for adaptive thermogenesis have been incorporated in a compartmental model of body weight and body composition regulation. This is used to provide a mechanistic explanation as to how, during weight recovery, they can operate simultaneously but in opposite directions--with activation of thermogenesis under non-specific control being energy-dissipating, while suppression of thermogenesis under adipose-specific control being energy-conserving--and could hence explain the paradox of a high efficiency of fat recovery co-existing with an overall state of enhanced thermogenesis and hypermetabolism. Elucidating the components of the adipose-specific control of thermogenesis (ie its sensors, signals and effector mechanisms) will have important implications for our understanding of body composition regulation, and hence for the development of more effective strategies in the management of cachexia and obesity.

Adipose Tissue↗
PubMed1999

The control of partitioning between protein and fat during human starvation: its internal determinants and biological significance.

Human subjects vary in the extent to which their body's protein and fat compartments are mobilized for fuel during starvation. Although an inverse association between the initial adiposity and the contribution of protein as fuel during starvation has been known for nearly a century, interest in the quantitative importance and functional significance of the initial percentage fat as a determinant of biological variation in energy-partitioning between protein and fat (and hence in determining the partitioning characteristic of the individual) is relatively recent. The present paper addresses these issues by revisiting the classic Minnesota experiment of semi-starvation and refeeding from a standpoint of system physiology. In a quantitative analysis of the relationship between the initial body composition (ration FAT0: fat-free mass (FFM)0) and the composition of weight loss (ratio delta FAT: delta FFM) in the thirty-two men in the Minnesota study, the arguments are put forward that the fraction of FFM lost when the fat stores reach total depletion is independent of the initial percentage fat, and that this fraction represents the 'dispensable' component of the protein compartment that is compatible with life (i.e. the protein energy-reserve, rp). The concepts are developed that (1) the initial percentage body fat (which reflects the initial ratio FAT0:FFM0) provides a 'memory of partitioning' which dictates the control of partitioning between protein and fat in such a way that both the protein energy-reserve (rp) and the fat energy-reserve (rf) each complete depletion simultaneously, a strategy that would ensure maximum length of survival during long-term food scarcity, and that (2) variability in the relative sizes of these two energy reserves (i.e. in rf:rp) could, in addition to the initial percentage fat, also contribute to human variability in energy-partitioning. The basic assumptions underlying this re-analysis of the Minnesota data, and the concepts that are derived from it, have been integrated in the simple mathematical model for predicting the partitioning characteristic of the individual. This model is used to explain how variability in the fraction of the protein compartment that could function as an energy reserve (rp) can be as important as the initial percentage fat in determining inter-individual variability in protein-sparing during the early phase of starvation, in fuel partitioning during prolonged starvation, or in the maximum percentage weight loss during starvation. The elucidation of factors underlying variability in the size of the protein energy-reserve may have important implications for our understanding of the pathophysiology of starvation and age-associated susceptibility to muscle wasting, and in the clinical management of cachexia and obesity.

Body Composition↗
PubMed1999

Low-protein overfeeding: a tool to unmask susceptibility to obesity in humans.

In search for an approach to identify physiological targets for therapeutic intervention in obesity management, we have revisited the classic human overfeeding studies of the 1960s, with new emphasis on a 'subgroup' of volunteers who were shifted between overfeeding on a typical affluent (normal-protein) diet and overfeeding on a low-protein diet. Following a re-analysis of these data, the arguments are put forward that since low-protein overfeeding is not only a potent stimulus of thermogenesis, but also an amplifier (or magnifier) of the small inter-individual variations in thermogenesis on the affluent (normal-protein) diet, it can be used as a tool to unmask some of the genetic and metabolic basis underlying human susceptibility to leanness and fatness.

Body Temperature Regulation↗
PubMed1998

Adaptive reduction in basal metabolic rate in response to food deprivation in humans: a role for feedback signals from fat stores.

We assessed the importance of lean and fat tissue depletion as determinants of the adaptive reduction in basal metabolic rate (BMR) in response to food deprivation by reanalyzing the data on BMR and body composition for the 32 men participating in the classic Minnesota experiment of semi-starvation and refeeding. We used individual data on BMR, body fat, and fat-free mass (FFM) assessed during the control (prestarvation) period, at weeks 12 and 24 of semistarvation (S12 and S24), and week 12 of restricted refeeding (R 12) to calculate an index of the reduction in thermogenesis at S12, S24, and R12, defined as the change in BMR adjusted for changes in FFM and fat mass, and an index of the state of depletion of the fat mass and FFM compartments at these times, defined as the deviation in fat mass or FFM relative to control values. The results indicated a positive relation between the reduction in thermogenesis and the degree of fat mass depletion (but not FFM depletion) during weight loss as well as during weight recovery (r = 0.5, P < 0.01). Furthermore, the residual variance was predicted by the initial (prestarvation) percentage fat and the cormic index (sitting height/height). Taken together, these results in normal-weight men responding to severe food deprivation reveal anthropometric predictors for human interindividual variability in the capacity for energy conservation and suggest that the adaptive reduction in BMR is partly determined by an autoregulatory feedback control system linking the state of depletion of fat stores to compensatory mechanisms that suppress thermogenesis.

Adipose Tissue↗
PubMed1997

Poststarvation hyperphagia and body fat overshooting in humans: a role for feedback signals from lean and fat tissues.

An increase in the sensation of hunger and overeating after a period of chronic energy deprivation can be part of an autoregulatory phenomenon attempting to restore body weight. To gain insights into the role of fat and lean tissue depletion as determinants of such a hyperphagic response in humans, we reanalyzed the individual data on food intake and body composition available for the 12 starved and refed men in the classical Minnesota Experiment after a shift from a 12-wk period of restricted refeeding to an ad libitum refeeding period of 8 wk. For each individual, the following were determined: 1) the total hyperphagic response during the ad libitum refeeding period, calculated as the energy intake in excess of that during the prestarvation (control) period; 2) the degree of fat recovery and that of fat-free-mass (FFM) recovery before ad libitum refeeding, calculated as the deviation in fat and FFM from their respective prestarvation values (ie, the amount of fat or FFM before ad libitum refeeding as a percentage of fat or FFM during the control period); and 3) the deficit in energy intake before ad libitum refeeding, calculated as the difference between the energy intake during the period of restricted refeeding and that during the control period. The results indicate that 1) the total hyperphagic response is inversely correlated with the degree of fat recovery (r = -0.6) as well as with that of FFM recovery (r = -0.5), 2) the correlation between hyperphagia and FFM recovery persists after adjustment for fat recovery, and 3) the correlations between hyperphagia and fat recovery or FFM recovery persist after adjustment for the variance in the energy deficit during the preceding period of restricted refeeding. Taken together, these results in humans suggest that poststarvation hyperphagia is determined to a large extent by autoregulatory feedback mechanisms from both fat and lean tissues. These findings, which have implications for both the treatment of obesity and for nutritional rehabilitation after malnutrition and cachexia, have been integrated into a compartmental model of autoregulation of body composition, and can be used to explain the phenomenon of poststarvation overshoot in body fat.

Adipose Tissue↗
PubMed1996

Highly supralinear feedback inhibition of Ca2+ uptake by the Ca2+ load of intracellular stores.

Net Ca2+ uptake into intracellular Ca2+ stores of homogenized cells is transient, even when the extravesicular Ca2+ concentration is kept constant. To study the mechanism underlying the phenomenon, we have investigated 45Ca2+ uptake by HL-60 cell homogenates. The initial rate of Ca2+ uptake as well as the final amount of stored Ca2+ were a function of the extravesicular Ca2+ concentration. However, Ca2+ uptake stopped independently of the extravesicular Ca2+ concentration after approximately 10 min. Studies using Ca2+-ATPase inhibitors demonstrated that the transient nature of the net uptake was not due to Ca2+ efflux. Monovalent cation ionophores did not influence the Ca2+ uptake curves, excluding a relevant involvement of pH and membrane potential. Together with the observation of a continued Ca2+ uptake in the presence of the intralumenal Ca2+ chelator oxalate, these results strongly suggest a feedback inhibition of Ca2+ uptake by the Ca2+ load of intracellular stores. The concentration-inhibition relationship between the Ca2+ load and the rate of Ca2+ uptake was highly supralinear (slope factor >/= 4). IC50 and maximum of the dose-inhibition curve, but not the slope factor were a function of the extravesicular free Ca2+ concentration. A series of three logistic equations derived from our data allowed an appropriate description of the behavior of Ca2+ uptake. Our results suggest, in addition to its well known activation by cytosolic Ca2+ concentration, a highly supralinear feedback inhibition of Ca2+ uptake by the Ca2+ load of intracellular stores. The steepness of the feedback inhibition might have a profound effect on spatial and temporal behavior of the Ca2+ signal.

Biological Transport↗
PubMed1996

Autoregulation of body composition during weight recovery in human: the Minnesota Experiment revisited.

OBJECTIVES: To gain insights into the control systems underlying human variability in the regulation of body composition during weight recovery, as well as the disproportionate recovery of fat relative to lean tissue, the classical Minnesota Experiment conducted on 32 men subjected to long-term semi-starvation and refeeding was revisited with the following objectives: (1) to determine whether the control of energy-partitioning between lean and fat tissues during weight loss and weight recovery is an individual characteristic, and if a predictor can be statistically identified, (2) to determine whether the reduction in thermogenesis during weight loss persists during weight recovery, and underlies the disproportionate recovery of fat tissue and (3) to integrate the control of energy-partitioning and that of thermogenesis in order to explain the pattern of lean and fat tissue mobilisation and deposition during weight loss and weight recovery. METHODS: Individual data on body weight, body fat, fat-free-mass (FFM), and basal metabolic rate (BMR), assessed during the control baseline period (i.e. prior to weight loss), at the end of 24 weeks of semi-starvation, and at the end of a 12 week period of restricted refeeding, were used to calculate the following parameters: (i) a quantitative index of energy-partitioning, the P-ratio, defined as the proportion of body energy mobilised as protein during weight loss, or as the proportion of body energy deposited as protein during weight recovery, (ii) a quantitative index of changes in thermogenesis, defined as the change in BMR adjusted for FFM (or for both FFM and fat mass) and (iii) the degree of replenishment of fat and FFM compartments, defined as the recovery of body fat and FFM (during refeeding) as a percentage of that lost during semi-starvation. RESULTS: This re-analysis indicates the following: (i) a large inter-individual variability in P-ratio during both weight loss and weight recovery, but for a given individual, the P-ratio during refeeding is strongly correlated with the P-ratio during semi-starvation, (ii) body composition during the control period is the most important predictor of variability in P-ratio, such that the higher the initial % body fat, the lower the proportion of energy mobilised as protein, and hence the greater the propensity to mobilise fat during semi-starvation and to subsequently deposit fat during refeeding and (iii) at week 12 of refeeding, the change in adjusted BMR is found to be reduced by a magnitude which is inversely proportional to the degree of fat recovery, but is unrelated to the degree of FFM recovery. A quantitative relationship is derived between the P-ratio during refeeding, the % fat recovery, and the P-ratio during semi-starvation. CONCLUSIONS: Evidence is presented here suggesting that (i) human variability in the pattern of lean and fat tissue deposition during weight recovery is to a large extent determined by individual variations in the control of energy-partitioning, for which the initial % body fat is the most important predictor and (ii) the disproportionate gain in fat relative to lean tissue during weight recovery is contributed by a reduction in thermogenesis (i.e. increased efficiency of food utilization) for accelerating specifically the replenishment of the fat stores. These control systems, operating via energy-partitioning and thermogenesis, have been integrated into a compartmental model for the regulation of body composition during underfeeding/refeeding, and can be used to explain the individual pattern of lean and fat tissue deposition during weight recovery in situations ranging from the rehabilitation after malnutrition to the relapse of obesity.

Adipose Tissue↗
PubMed1996

Dissociation of systemic GH-IGF-I axis from a genetic basis for short stature in African Pygmies.

OBJECTIVES: To test the hypothesis that the primary cause of short stature in African Pygmies resides in low levels of insulin-like growth factor I (IGF-I), and to evaluate whether any observed alterations in their systemic IGF-I status can be dissociated from the effects of malnutrition and/or altered immune status. SETTING: Expedition to camps of partially sedentarized African Pygmies and neighbouring Bantu farmers living in the equatorial rain forest of Eastern Cameroon. DESIGN: Serum assays for hormonal and immune status were conducted for individuals (children, adolescents, young and old adults) showing no overt clinical nor biochemical signs of malnutrition, as judged from anthropometry, clinical examinations and serum assays of albumin, pre-albumin, retinol-binding protein, transferrin, iron, zinc, magnesium and calcium. RESULTS: African Pygmies did not differ from Europeans or Bantus in mean serum IGF-I concentrations, nor in the relationship between serum IGF-I and its major binding protein (IGFBP-3). However, although in both African groups the immunoglobulins IgG, IgM and IgE as well as the C-reactive protein and ceruloplasmin were above the normal range of European references, the Pygmies differed from their Bantu neighbours in their much higher IgG and IgM serum levels. A plot of serum IGF-I against these immunoglobulins in Pygmies revealed a reverse sigmoidal relationship, with the low IGF-I values associated with serum levels of IgG and IgM which clearly exceeded those found in the Bantus. CONCLUSIONS: This study indicates that in growing and adult African Pygmies showing no clinical nor biochemical signs of nutritional deficiency, serum IGF-I and IGFBP-3 (hence IGF-I bioavailability to its receptors) are essentially normal, and that low circulating levels of IGF-I in Pygmies reside in differential exposure and/or responsiveness to environmental challenge (e.g. infections) rather than in an inherited defect in the systemic growth-hormone (GH)-IGF-I axis.

Adolescent↗
PubMed1995

Highly cooperative Ca2+ elevations in response to Ins(1,4,5)P3 microperfusion through a patch-clamp pipette.

To study the initial kinetics of Ins(1,4,5)P3-induced [Ca2+]i elevations with a high time resolution and to avoid the problem of cell-to-cell heterogeneity, we have used the combined patch-clamp/microfluorimetry technique. The mathematical description of the microperfusion of Ins(1,4,5)P3 and the subsequent Ca2+ release consists of a monoexponential decay (cytosolic Ins(1,4,5)P3 concentration) and a Hill equation (Ins(1,4,5)P3 dose-response curve). Two additional Hill equations and an integration were necessary to include a putative dependence of Ins(1,4,5)P3-induced Ca2+ release on [Ca2+]i. Best-fitting analysis assuming [Ca2+]i-independent Ca2+ release yielded Hill coefficients between 4 and 12. The high cooperativity was also observed with the poorly metabolizable analog Ins(2,4,5)P3 and was independent of extracellular [Ca2+]. Best-fitting analysis including a positive [Ca2+]i feedback suggested a cooperativity on the level of Ins(1,4,5)P3-induced channel opening (n = 2) and an enhancement of Ins(1,4,5)P3-induced Ca2+ release by [Ca2+]i. In summary, the onset kinetics of Ins(1,4,5)P3-induced [Ca2+]i elevations in single HL-60 granulocytes showed a very high cooperativity, presumably because of a cooperativity on the level of channel opening and a positive Ca2+ feedback, but not because of Ca2+ influx or Ins(1,4,5)P3 metabolism. This high cooperativity, acting in concert with negative feedback mechanisms, might play an important role in the fine-tuning of the cellular Ca2+ signal.

Calcium↗
PubMed1993

Space and time characteristics of transmitter release at the nerve-electroplaque junction of Torpedo.

1. A loose patch electrode was used to stimulate axon terminals and to record evoked electroplaque currents (EPCs) in a limited area of innervated membrane of the electric organ of Torpedo marmorata. Electrophysiological signals were compared to the predictions of a semi-quantitative model of synaptic transmission which was designed to simulate the release of several packets of neurotransmitter molecules, at the same or at different sites of the synapse, synchronously or with various temporal patterns. 2. The amplitude distribution of EPCs evoked by activation of nerve terminals showed quantal steps. The time to peak of EPCs was in most cases independent of amplitude, but in their decaying phase a positive correlation was seen between half-decay time and amplitude. Comparison with the model suggested that (i) a dynamic interaction occurred at the end of the EPC between the fields of postsynaptic membrane activated by individual quanta, and (ii) the sites of quantal release in the electric organ are separated from each other by 600-1000 nm. 3. Spontaneous miniature electroplaque potentials (MEPPs) were recorded externally with the same type of loose patch electrode. The majority (75%) of external MEPPs displayed a homogeneous and rapid time course. This fast MEPP population had a mean time to peak of 0.43 ms, a half-decay time of 0.45 ms and a time constant of decay of 0.35 ms. 4. Despite homogeneous characteristics of time course, fast MEPPs exhibited a wide amplitude distribution with a main population which could be fitted by a Gaussian curve around 1 mV, and another population of small amplitude. Both the time-to-peak and the half-decay time of fast MEPPs showed a positive correlation with the amplitude from the smallest to the largest events. Acetylcholinesterase was not blocked. 5. In addition to the fast MEPPs, spontaneous signals exhibiting a slow rate of rise, or a slow rate of decay, or both were observed. They occurred at any time during the experiment, independently of the overall frequency. Approximately 15% of the total number of events had a slow rise but their decay phase was nevertheless rapid and could be ascribed to the kinetics of receptors. These slow-rising MEPPs exhibited a variety of conformations: slow but smooth rise, sudden change of slope and sometimes several bumps or inflexions. Their average amplitude was significantly smaller than that of the main population of fast MEPPs. 6. Composite MEPPs with multiple peaks as well as bursts of small MEPPs were often encountered, even during periods of low frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1986

Energy cost of walking and exertional dyspnea in multiple sclerosis.

Pulmonary functions at rest and cardiorespiratory responses to low speed treadmill walking were investigated in 24 patients (P), (mean age, 38 years; range, 20 to 56 yr) with multiple sclerosis and compared with a control group (C). The following parameters were significantly (p less than 0.01) different in P from those in C. At rest in P, the residual volume to TLC ratio was 21% greater, respiratory muscle strength index was 28% lower, and heart rate (HR) was 11 beats/min-1 higher. During treadmill walking at a given speed, HR, minute ventilation (VE), and O2 consumption (VO2) were all elevated (37 to 119%). In addition, the energy cost of walking, per unit distance, above resting, was 2 to 3 times greater, with mean +/- SEM values for P of 0.299 +/- 0.019 and C of 0.147 +/- 0.006 at 2 km/h and 0.275 +/- 0.042 and 0.110 +/- 0.005 (for P and C, respectively) ml O2 kg-1 m-1 at 4 km/h; the HR and VE/VO2, also when referred to a given VO2, were higher. We conclude that a high energy cost of walking may be an important contributing factor to breathlessness and leg fatigue in patients with multiple sclerosis. Poor conditioning, altered cardiovascular control, and respiratory muscle weakness may play additional roles.

Adult↗
PubMed1986

[Not Available].

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France↗