Effect of dietary restraint during and following pegylated recombinant leptin (PEG-OB) treatment of overweight men

Lejeune, M.P.G.M.; Hukshorn, Chris J.; Saris, W.H.M.; Westerterp-Plantenga, Margriet S.

doi:10.1038/sj.ijo.0802431

Cited by 37 publications

(30 citation statements)

References 34 publications

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“…37 A period of 6-week treatment by leptin/VLCD, similarly to our 4-week VLCD trial, 5 lead to an increase in cognitive restraint score and to a significant decrease in both disinhibition and hunger scores. The decrease in hunger score during the leptin treatment was Weight loss predictors in sibutramine treated obese women V Hainer et al positively related to body weight loss.…”

Section: Discussionmentioning

confidence: 53%

“…However, the decrease in disinhibition score during the treatment period positively correlated with the weight loss in the placebo group and not in the leptintreated group. 37 Among the recorded changes in behavioral and nutritional parameters over the study, our results revealed the unique role of change in disinhibition score, which remained the sole significant factor related to the BMI decrease at month 12. The association of sibutramine-induced weight loss with a decline in disinhibition might be related to the previously shown positive impact of sibutramine treatment on obesityrelated health risks.…”

Section: Discussionmentioning

confidence: 64%

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Psychobehavioral and nutritional predictors of weight loss in obese women treated with sibutramine

et al. 2004

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OBJECTIVE:To reveal whether baseline body mass index (BMI), and psychobehavioral and nutritional markers were significant predictors of the change in BMI observed after 4 and 12 months in obese women enrolled in a weight reduction program, including low-energy diet, increased physical activity, cognitive behavior therapy and sibutramine. The impact of changes in psychobehavioral and nutritional markers observed after 4 and 12 months of treatment on BMI changes was also investigated. DESIGN: During a double-blind placebo-controlled 4-month period, subjects received either sibutramine (10 mg/day) or placebo. Then, an open phase with sibutramine administered to all patients continued until month 12. SUBJECTS: In total, 80 obese women (age: 43.9710.6 y, BMI: 36.774.8 kg/m 2 ). MEASUREMENTS: The dependent variable was change in BMI while baseline BMI, mode of treatment, the Beck depression score, the three items (dietary restraint, disinhibition and perceived hunger) of the Eating Inventory (EI), energy and macronutrient intakes were independent variables. At 1-week dietary records were analyzed using a computer software for assessing energy and macronutrient intake. RESULTS: Multiple regression analysis revealed that the BMI loss at month 4 was significantly influenced by mode of treatment and initial BMI, whereas a borderline negative relationship was observed with the baseline restraint score. Baseline BMI, depression score, restraint score and total energy intake predicted weight loss at month 12. These predictive variables accounted for 43.8% of the variance in BMI loss at 12 months. When relationships between the BMI loss and changes in all included psychobehavioral and nutritional parameters were considered after 12 months of treatment, a drop in the disinhibition score of the EI appeared the only significant factor affecting the BMI decrease. CONCLUSIONS: Our results suggest that psychobehavioral and nutritional characteristics can be used as predictors of weight loss in response to a comprehensive weight management program including pharmacological treatment with sibutramine.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 64%

Psychobehavioral and nutritional predictors of weight loss in obese women treated with sibutramine

et al. 2004

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“…The authors suggested this was due to decreased insulin-mediated glucose metabolism in adipose tissue, and that decreased postprandial exposure of leptin resulting from a fat bolus could be adipogenic (Havel et al, 1999), citing the hyperphagia and gross obesity resultant in humans from genetic impairment of leptin production (Montague et al, 1997). Whether a decrease in circulating leptin over 24 h may represent an adverse risk for obesity remains controversial and recombinant leptin weight loss therapy in hyperleptinaemic obese subjects has been met with limited success (Hukshorn et al, 2002;Fogteloo et al, 2003;Lejeune et al, 2003;Wong et al, 2004). It has been suggested that the role of leptin is not prevention of obesity, rather a response to low-energy availability (Havel, 2004) such that during starvation leptin falls triggering an increase in hunger .…”

Section: Discussionmentioning

confidence: 99%

Effect of high-fat meals and fatty acid saturation on postprandial levels of the hormones ghrelin and leptin in healthy men

et al. 2005

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Objective: Ghrelin and leptin play a role in control of food intake and adiposity but mechanisms regulating these hormones in man are poorly defined and evidence that dietary fats may have adverse effects is inconclusive. We investigated whether high-fat meals, which differed in saturated fatty acid (SFA) content acutely modified these hormones. Design: Randomised, double-blind, crossover trial. A high-fat (HF) test meal (5974 g fat; 71% of energy as fat) was given for breakfast on two occasions. Meals comprised either high (B70:30) or low (B55:45) saturated:unsaturated fatty acid (SFA:USFA) ratio. Fasting and postprandial measurements of serum total ghrelin (RIA), leptin (enzyme-linked immunosorbent assay (ELISA)) and insulin (RIA) were made over 6 h. Postprandial measurements were also made at 10 and 24 h following a fat-exclusion lunch, snack and dinner. Subjects: A total of 18 lean, healthy men. Results: There was no significant effect of the fatty meal (time, P40.05), nor a differential effect of SFA:USFA ratio (treatment * time, P40.05) on ghrelin over 6 h. Leptin decreased in response to both HF treatments (time, Po0.001) but increased SFA content did not further inhibit hormone secretion (treatment * time, P40.05). There was no significant correlation between ghrelin or leptin and circulating insulin (P40.05). Conclusion:We conclude that HF diets may adversely effect serum leptin, although the circadian decrease may account in part for this response. Increasing dietary SFAs had no deleterious effects on leptin or total ghrelin.

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“…Initial attempts to utilize leptin as a monotherapy for obesity included using supraphysiological doses of leptin (75,103,147); however, data from these trials revealed modest, if any, weight loss and with significant variability among the participants. In a small, proofof-concept, phase II clinical trial, Heymsfield et al (103) administered leptin in escalating doses to obese participants for up to 24 wk.…”

Section: Leptin Excess Due To Leptin Resistance or Tolerance In Humanmentioning

confidence: 99%

Leptin in human physiology and pathophysiology

Mantzoros

Magkos

Brinkoetter

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

510

322

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Leptin, discovered through positional cloning 15 years ago, is an adipocyte-secreted hormone with pleiotropic effects in the physiology and pathophysiology of energy homeostasis, endocrinology, and metabolism. Studies in vitro and in animal models highlight the potential for leptin to regulate a number of physiological functions. Available evidence from human studies indicates that leptin has a mainly permissive role, with leptin administration being effective in states of leptin deficiency, less effective in states of leptin adequacy, and largely ineffective in states of leptin excess. Results from interventional studies in humans demonstrate that leptin administration in subjects with congenital complete leptin deficiency or subjects with partial leptin deficiency (subjects with lipoatrophy, congenital or related to HIV infection, and women with hypothalamic amenorrhea) reverses the energy homeostasis and neuroendocrine and metabolic abnormalities associated with these conditions. More specifically, in women with hypothalamic amenorrhea, leptin helps restore abnormalities in hypothalamic-pituitary-peripheral axes including the gonadal, thyroid, growth hormone, and to a lesser extent adrenal axes. Furthermore, leptin results in resumption of menses in the majority of these subjects and, in the long term, may increase bone mineral content and density, especially at the lumbar spine. In patients with congenital or HIVrelated lipoatrophy, leptin treatment is also associated with improvements in insulin sensitivity and lipid profile, concomitant with reduced visceral and ectopic fat deposition. In contrast, leptin's effects are largely absent in the obese hyperleptinemic state, probably due to leptin resistance or tolerance. Hence, another emerging area of research pertains to the discovery and/or usefulness of leptin sensitizers. Results from ongoing studies are expected to further increase our understanding of the role of leptin and the potential clinical applications of leptin or its analogs in human therapeutics. adipokines; adipose tissue; leptin resistance; leptin deficiency; hypoleptinemia STUDIES OF GENETICALLY OBESE MICE serendipitously found in the Jackson Laboratories revealed that their phenotypes derive from homozygous mutations of either the obese (ob) or diabetic (db) genes that result in obesity and insulin resistance or diabetes as well as endocrine and immune dysfunction (53, 54,115,117,183,261). The gene mutation in the ob/ob mouse results in a complete deficiency of or a truncated and biologically inactive ob gene product (287); the latter subsequently was given the name leptin (95), from the Greek word "leptos" (meaning "thin"), because when this protein was given to the obese ob/ob mice they lost significant amounts of body weight. It was then recognized that the db gene codes for the leptin receptor (140). Consequently, exogenously administered leptin reduces body weight and resolves the metabolic, endocrine, and immune disturbances in ob/ob mice but has no effects in db/db mice (100, 111, 28...

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Effect of dietary restraint during and following pegylated recombinant leptin (PEG-OB) treatment of overweight men

Cited by 37 publications

References 34 publications

Psychobehavioral and nutritional predictors of weight loss in obese women treated with sibutramine

Psychobehavioral and nutritional predictors of weight loss in obese women treated with sibutramine

Effect of high-fat meals and fatty acid saturation on postprandial levels of the hormones ghrelin and leptin in healthy men

Leptin in human physiology and pathophysiology

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