Uninephrectomy in rats on a fixed food intake potentiates both anorexia and circulating cytokine subsets in response to LPS

Recent human studies have suggested that mild reduction in kidney function can alter immune response and increase susceptibility to infection. The role of mild reduction in kidney function in altering susceptibility to bacterial lipopolysaccharide (LPS) responses was investigated in uninephrectomized rats compared to Sham-operated controls rats 4 weeks after surgery. Throughout the 4 weeks, all rats were maintained under mild food restriction at 90% of ad libitum intake to ensure the same caloric intake in both groups. In comparison to Sham, uninephrectomy (UniNX) potentiated LPS-induced anorexia by 2.1-fold. The circulating anorexigenic cytokines granulocyte-macrophage colony stimulating factor, interferon-γ, tumor necrosis factor-α, and complement-derived acylation-stimulating protein were elevated after LPS in UniNX animals compared to Sham animals. Interleukin(IL)1β and IL6 pro-inflammatory cytokines were transiently increased. Anti-inflammatory cytokines IL4 and IL10 did not differ or had a tendency to be lower in UniNX group compared to Sham animals. LPS-induced anorexia was associated with increased anorexigenic neuropeptides mRNA for pro-opiomelanocortin, corticotrophin-releasing factor, and cocaine–amphetamine-regulated transcript in the hypothalamus of both Sham and UniNX groups, but at higher levels in the UniNX group. Melanocortin-4-receptor mRNA was markedly increased in the UniNX group, which may have contributed to the enhanced anorexic response to LPS of the UniNX group. In summary, UniNX potentiates pro-inflammatory cytokine production, anorexia, and selected hypothalamic anorexigenic neuropeptides in response to LPS

P-322: Alterations in blood pressure and heart rate during cyclic changes in food intake

In people trying to loose body weight, cycles of hypophagia followed by hyperphagia are quite common. The aim of the present study was to evaluate the alterations in daily mean arterial pressure (MAP) and heart rate (HR) during short-term (5-day) changes in food intake. Adult male lop-eared rabbits were instrumented for continuous measurement of blood pressure and HR by telemetry (24 hours/day) and fed 150 g/day of maintenance diet. The animals were subjected to five 14-day periods. Each period consisted of 5 days where food intake (normal chow) was randomly set to either 225 g (+50 %), 187 g (+25 %), 112 g (-25 %), 75 g (-50 %) per day or ad libitum, followed by 9 days of recovery at 150 g/day. A 50 % increase in food intake induced an immediate and significant increase in HR and a slight increase in MAP (+24.7 ± 2.8 bpm and +2.2 ± 0.6 mmHg at day 5). Similarly, a 50 % decrease in food intake induced a decrease in HR and MAP (-29.0 ± 1.8 bpm and -5.9 ± 1.3 mmHg at day 5). Food access ad libitum induced an even more pronounced increase in HR and MAP (+43.3 ± 3.9 bpm and +4.4 ± 0.8 mmHg at day 5). Unlike the increase in HR during hyperphagia which reached plateau after 1 day, the decrease in HR during hypophagia was progressive (-29.0 ± 1.8 on day 5 vs. -17.2 ± 2.1 bpm on day 1 of -50 %). The effect of hyperphagia on MAP and HR was reversible within 1 day, except after food ad libitum. Recovery of MAP and HR following hypophagia was rapid, but not complete. Our data suggest that short-term quantitative variations in food intake can lead to pronounced changes in daily hemodynamics, with different courses for hyper- vs. hypophagia. These alterations may play an important role in explaining the increased cardiovascular morbidity associated with weight cyclin

Pathways from dieting to weight regain, to obesity and to the metabolic syndrome: an overview

Every year, scores of millions of people – as diverse as obese and lean, teenagers and older adults, sedentary and elite athletes, commoners and celebrities – attempt to lose weight on some form of diet. They are often encouraged by their parents, friends, health professionals, training coaches, a media that promotes a slim image and a diet- industry that in Europe and United States alone has an annual turnover in excess of $150 billion. Weight regain is generally the rule, with one-third to two-thirds of the weight lost being regained within 1 year and almost all is regained within 5 years. With studies of the long-term outcomes showing that at least one-third of dieters regain more weight than they lost, together with prospective studies indicating that dieting during childhood and adolescence predicts future weight gain and obesity, there is concern as to whether dieting may paradoxically be promoting exactly the opposite of what it is intended to achieve. Does dieting really make people fatter? How? Does dieting increase the risks for cardiometabolic diseases as many go through repeated cycles of intentional weight loss and unintentional weight regain, i.e. through yo-yo dieting or weight cycling? What's new in adipose tissue biology pertaining to the mechanisms that drive weight regain? Why does exercise not necessarily work in concert with dieting to achieve weight loss and prevent weight regain? What ‘lessons’ are we learning from bariatric surgery about the mechanisms by which long-term weight loss seems achievable? It is these questions, against a background of preoccupation with dieting, that recent advances and controversies relevant to the theme of ‘Pathways from dieting to weight regain, to obesity and to the metabolic syndrome’ are addressed in this overview and the eight review articles in this supplement reporting the proceedings of the 7th Fribourg Obesity Research Conference

How dieting makes some fatter: from a perspective of human body composition autoregulation

Dieting makes you fat – the title of a book published in 1983 – embodies the notion that dieting to control body weight predisposes the individual to acquire even more body fat. While this notion is controversial, its debate underscores the large gap that exists in our understanding of basic physiological laws that govern the regulation of human body composition. A striking example is the key role attributed to adipokines as feedback signals between adipose tissue depletion and compensatory increases in food intake. Yet, the relative importance of fat depletion per se as a determinant of post-dieting hyperphagia is unknown. On the other hand, the question of whether the depletion of lean tissues can provide feedback signals on the hunger–appetite drive is rarely invoked, despite evidence that food intake during growth is dominated by the impetus for lean tissue deposition, amidst proposals for the existence of protein–static mechanisms for the regulation of growth and maintenance of lean body mass. In fact, a feedback loop between fat depletion and food intake cannot explain why human subjects recovering from starvation continue to overeat well after body fat has been restored to pre-starvation values, thereby contributing to ‘fat overshooting’. In addressing the plausibility and mechanistic basis by which dieting may predispose to increased fatness, this paper integrates the results derived from re-analysis of classic longitudinal studies of human starvation and refeeding. These suggest that feedback signals from both fat and lean tissues contribute to recovering body weight through effects on energy intake and thermogenesis, and that a faster rate of fat recovery relative to lean tissue recovery is a central outcome of body composition autoregulation that drives fat overshooting. A main implication of these findings is that the risk of becoming fatter in response to dieting is greater in lean than in obese individuals.</jats:p

How dieting makes some fatter: from a perspective of human body composition autoregulation

Dieting makes you fat - the title of a book published in 1983 - embodies the notion that dieting to control body weight predisposes the individual to acquire even more body fat. While this notion is controversial, its debate underscores the large gap that exists in our understanding of basic physiological laws that govern the regulation of human body composition. A striking example is the key role attributed to adipokines as feedback signals between adipose tissue depletion and compensatory increases in food intake. Yet, the relative importance of fat depletion per se as a determinant of post-dieting hyperphagia is unknown. On the other hand, the question of whether the depletion of lean tissues can provide feedback signals on the hunger-appetite drive is rarely invoked, despite evidence that food intake during growth is dominated by the impetus for lean tissue deposition, amidst proposals for the existence of protein-static mechanisms for the regulation of growth and maintenance of lean body mass. In fact, a feedback loop between fat depletion and food intake cannot explain why human subjects recovering from starvation continue to overeat well after body fat has been restored to pre-starvation values, thereby contributing to ‘fat overshooting'. In addressing the plausibility and mechanistic basis by which dieting may predispose to increased fatness, this paper integrates the results derived from re-analysis of classic longitudinal studies of human starvation and refeeding. These suggest that feedback signals from both fat and lean tissues contribute to recovering body weight through effects on energy intake and thermogenesis, and that a faster rate of fat recovery relative to lean tissue recovery is a central outcome of body composition autoregulation that drives fat overshooting. A main implication of these findings is that the risk of becoming fatter in response to dieting is greater in lean than in obese individual

Short-term (5-day) changes in food intake alter daily hemodynamics in rabbits

Background: In humans, particularly among individuals trying to lose weight, cycles of hypophagia followed by cycles of hyperphagia are quite common and may lead to an increased cardiovascular morbidity. The aim of the present study was to evaluate the alterations in daily mean arterial pressure (MAP) and heart rate (HR) during short-term (5-day) changes in food intake. Methods: Adult male rabbits instrumented for continuous (24 h/day) telemetric recording of blood pressure (BP) and HR were subjected to five 14-day periods of altered food intake. Each period consisted of 5 days in which food intake was set to −50%, −25%, +25%, +50%, or +100% (food ad libitum) per day followed by 9 days at 150 g/day of maintenance diet. Results: The increase in food intake induced an immediate and significant increase in HR and a less pronounced increase in MAP. Similarly, a 25% and 50% decrease in food intake induced a decrease in HR and MAP. Unlike the increase in HR during hyperphagia, which reached a plateau after 1 day, the decrease in HR during hypophagia was progressive. The effect of hyperphagia on MAP and HR was reversible within 1 day, whereas hypophagia induced changes were persistent over several days. Conclusions: A highly significant linear relationship can be established across the alterations in food intake (from −50% to +100%) and the respective changes in blood pressure (BP) or HR. These data suggest that prompt changes in hemodynamics induced by alterations in food intake might be implicated in the early events during weight gain or during weight loss. Am J Hypertens 2003;16:302-306 @ 2003 American Journal of Hypertension, Lt

Cardiovascular and cutaneous responses to the combination of alcohol and soft drinks: the way to orthostatic intolerance?

Aim. Acute ingestion of alcohol is often accompanied by cardiovascular dysregulation, malaise and even syncope. The full hemodynamic and cutaneous responses to the combination of alcohol and sugar (i.e. alcopops), a common combination in young people, and the mechanisms for the propensity to orthostatic intolerance are not well established. Thus, the purpose of this study was to evaluate the cardiovascular and cutaneous responses to alcopops in young subjects. Methods. Cardiovascular and cutaneous responses were assessed in twenty-four healthy young subjects (twelve men, twelve women) sitting comfortably and during prolonged active standing with a 30-min baseline and 130min following ingestion of 400mL of either: water, water+48g sugar, water+vodka (1.28mL.kg-1 of body weight, providing 0.4g alcohol.kg-1), water+sugar+vodka, according to a randomized cross-over design. Results. Compared to alcohol alone, vodka+sugar induced a lower breath alcohol concentration (BrAC), blood pressure and total peripheral resistance (p<0.05), a higher cardiac output and heart rate (p<0.05) both in sitting position and during active standing. In sitting position vodka+sugar consumption also led to a greater increase in skin blood flow and hand temperature (p<0.05) and a decrease in baroreflex sensitivity (p<0.05). We observed similar results between men and women both in sitting position and during active standing. Conclusion. Despite lower BrAC, ingestion of alcopops induced acute vasodilation and hypotension in sitting position and an encroach of the hemodynamic reserve during active standing. Even if subjects did not feel any signs of syncope these results could be of clinical importance with higher doses of alcohol or if combined to other hypotensive challenges

Serial changes in cardiovascular and renal function of rabbits ingesting a high-fat, high-calorie diet

To explore the mechanisms of obesity-induced hypertension we analyzed the sequential changes in cardiovascular and renal function in adult rabbits switched to high-fat diet (HFD) for 8 weeks. Animals were housed in metabolic cages for continuous 24-h recording of arterial pressure by telemetry and daily urine collection. High-fat diet induced a progressive increase in body weight (+47%) and a rapid rise in mean arterial pressure, heart rate, and glomerular filtration rate that stabilized, respectively, at 14%, 31% and 68% greater than control values. Time-course analysis of changes in blood pressure may reveal two components of obesity-induced hypertension, an early phase related to HFD itself and a later phase related to weight gain. Am J Hypertens 1999;12:826-829 © 1999 American Journal of Hypertension, Lt