Leptin administration does not prevent the bone mineral metabolism changes induced by weight loss

The objective was to examine the effects of weight loss and leptin administration following weight loss on calciotropic hormones and bone turnover. This was a prospective, single-blinded study of 12 subjects (8 women, 4 men; 2 nonobese, 10 obese; age range, 19-46 years) who were studied on an inpatient basis while maintaining their usual weight [Wt_initial] and during maintenance of 10% weight loss while receiving twice-daily injections of either a placebo [Wt_−10%P] or replacement doses of leptin [Wt_−10%L]. The main outcome measures were markers of bone formation (bone alkaline phosphatase and procollagen type 1 amino terminal propeptide) and resorption (N-telopeptide) as well as parathyroid hormone, calcium, and 25-hydroxy vitamin D measured from fasting morning serum. As expected, serum leptin declined with weight loss. Bone alkaline phosphatase decreased by 12.3% ± 3.9% between Wt_initial and Wt_−10%P and remained suppressed after leptin administration (both P < .01 compared with baseline). N-telopeptides increased by 37.2% ± 11.3% from Wt_initial to Wt_−10%L (P < .01). Procollagen type 1 amino terminal propeptide, parathyroid hormone, calcium, and 25-hydroxy vitamin D did not change. These results suggest that both decreased bone formation and increased bone resorption underlie bone loss associated with weight loss. Leptin administration did not prevent the uncoupling of bone remodeling that accompanies weight loss.     

L-tryptophan does not increase weight loss in carbohydrate-craving obese subjects

Eight subjects, aged 26 to 50 years, who had long histories of carbohydrate (CHO) craving and were more than 45 kg above desirable body weight participated in a randomized, double-blind, crossover pilot study on the effects of L-tryptophan on weight loss and mood state. One g of tryptophan with 10 g of CHO was administered three times a day, 30 min before meals, as an adjunct to a weight-loss protocol that included nutritional consultation teaching low fat, high fiber diets ranging from 1200-1600 kcals/day, behavior modification, and supportive therapy. During the pretreatment period, body weight and plasma tryptophan levels were measured and the Beck Depression Inventory, SCL 90 rating, and Profile-of-Mood State (POMS) were used to assess mood. During the treatment periods, subjects kept daily records of food intake and the timing of medication. All patients were seen at least biweekly. After six weeks on medication, baseline measurements were repeated and the crossover between tryptophan and placebo was implemented. After an additional six weeks on placebo or tryptophan, the same measurements were repeated. For the eight patients who completed the three-month protocol, the mean weight loss for six weeks on placebo was 1.14 kg and for six weeks on tryptophan was 2.3 kg. Mean Beck scores were 8.8 during the control period, 8.3 on placebo, and 10.9 on tryptophan. Mean SCL 90 ratings were 69.2 during the control, 54.6 on placebo, and 64.2 on tryptophan. Mean scores for total mood disturbance on the POMS were 48 during the control period, 43 on placebo, and 52 on tryptophan.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment with vitamin D or its analogues does not change body weight or blood glucose level in postmenopausal women

It has recently been stated that vitamin D analogues can reduce body weight in animal models. We evaluated the effect of treatment with vitamin D metabolites on the nutritional status of 238 postmenopausal women, who were participating in three double-blind placebo-controlled trials, the aim of which was to prevent or treat postmenopausal bone loss. After two years of treatment with vitamin D3, 2000 IU daily (n = 25), or l alpha OHD3, 0.25 micrograms daily (n = 23), or 1 year of treatment with 1,25 (OH)2D3, 0.25-0.50 micrograms daily (n = 40), no change in body weight or blood glucose level could be detected when compared to corresponding placebo treated groups (n = 150). It is concluded that the effect of vitamin D analogues on body weight is a phenomenon which is specific for an animal model and does not occur in man.     

Administration of physiologic levels of triiodothyronine increases leptin expression in calorie-restricted obese rats, but does not influence weight loss

Obesity has become a major public health problem, most commonly treated via dietary restriction to promote weight loss. Although leptin and thyroid hormones are involved in the regulation of energy balance, the role of these hormones after the stabilization of weight loss remains unclear. This study was designed to analyze the effect of thyroid hormone on sustained weight loss and leptin gene expression in obese animals after a loss of 5% to 10% of body weight. Thirty-day-old male Wistar rats were separated into 4 groups: control, obese, calorie restriction (CR), and calorie restriction with triiodothyronine administration (CRT). The obese group had increased weight and adiposity, leptin and insulin levels, and leptin gene expression. Dietary restriction in the CR group resulted in decreased body weight and adiposity, diminished leptin, and increased thyroid hormone receptor β expression. The CRT group, submitted to dietary restriction with concomitant administration of a physiologic triiodothyronine dose, had thyroid hormone receptor β expression at levels comparable with those observed in the control group and simultaneously increased leptin expression as compared with that in the CR group, suggesting that thyroid hormone modulates leptin expression under conditions of calorie restriction. Increased leptin expression in the CRT group did not result in increased circulating leptin or a statistically significant reduction in body weight during the treatment period. These data provide impetus for further study, as a longer treatment period may result in increased circulating leptin and, thus, further reduction in body weight during calorie restriction in an obesity model.     

Neutropenia does not prevent etodolac- or indomethacin-induced gastrointestinal damage in the rat

Neutrophils have been implicated in the acute formation of gastric mucosal erosions induced by nonsteroidal antiinflammatory drugs. The aims of the present study were to determine, in rats, the role of neutrophils in the pathogenesis of etodolac- and indomethacin-induced gastrointestinal ulceration and blood loss. Both drugs caused gastrointestinal ulceration, which was associated with increased blood loss, a rise in plasma haptoglobin concentration, and a rise in the number of circulating neutrophils. A marked infiltration of neutrophils occurred only in ileal tissue. Pretreatment with a selective antineutrophil serum induced a significant neutropenia, which failed to inhibit either etodolac- or indomethacin-induced gastrointestinal ulceration and blood loss. A further study demonstrated that the antineutrophil serum did not prevent gastric erosions induced by indomethacin, but it inhibited carrageenan paw edema, which is dependent, in part, on neutrophil infiltration and activation. It is concluded that neutrophils do not contribute to gastrointestinal ulceration and blood loss induced by nonsteroidal antiinflammatory drugs. Furthermore, in contrast with previous studies, our results provide no evidence that neutrophils contribute to indomethacin-induced acute gastric erosion formation.     

Add-back medrogestone does not prevent bone loss in premenopausal women treated with goserelin.

To investigate the effect of medrogestone on bone mineral density (BMD) and bone turnover under conditions of estrogen withdrawal, premenopausal women with endometriosis were treated with goserelin (Zoladex), combined with either placebo (group A, n = 12) or 10 mg medrogestone (Prothil, group B, n = 11) for six months, and followed for an additional six months. Lumbar spine BMD was measured at 0 and 6 month. Markers of bone turnover were serum bone alkaline phosphatase (sBAP) and osteocalcin (sOC) by ELISA, and urinary total pyridinoline (uPYD) and deoxypyridinoline crosslinks (uDPD) by HPLC. Patients in both groups had a similar and significant decrease in BMD after 6 months (4%, p < 0.01). The time course of changes in bone turnover, in contrast, was different in both groups. In group A, crosslink excretion increased from one month onwards, while no changes were seen in group B. In group A, sBAP levels rose during treatment, while in group B, this rise was delayed until treatment was terminated. Additionally, group B showed an initial suppression of sBAP and sOC. In both groups, sOC increased after treatment was discontinued. Medrogestone at 10 mg/d does not prevent lumbar bone loss in premenopausal women under estrogen deprivation. In the medrogestone add back group, the changes in bone turnover are compatible with low turnover bone loss,as ooposed to a state of high turnover seen in the unopposed goserelin group. This effect may be due to glucocorticoid receptor mediated actions of medrogestone on bone.     

The effect of body weight and weight loss on thyroid volume and function in obese women

OBJECTIVE: Thyroid volume and thyroid function may vary in obese and nonobese women. It is not known whether weight loss could affect thyroid volume and function in obese subjects. PATIENTS AND METHODS: The study population consisted of 98 premenopausal euthyroid obese [body mass index (BMI) = 30 kg/m2] women (mean age 40.5 +/- 11.4 years) and 31 nonobese (BMI < 25 kg/m2) women (mean age 38.6 +/- 12.9 years). Weight, height, BMI, waist circumference, body fat percentage and fat weight of all subjects were measured. Thyroid function and thyroid ultrasonography were performed at baseline and after 6 months of obesity treatment. Subgroup analysis was done according to weight loss. RESULTS: Thyroid volume (P = 0.021) and TSH concentration (P = 0.047) were higher; free T3 (P < 0.001) and free T4 concentrations (P = 0.045) were lower in obese women; however, all were still in the normal range. There was a positive correlation between thyroid volume and body weight (r = 0.319, P = 0.002), BMI (r = 0.504, P < 0.001), body fat percentage (r = 0.375, P = 0.001), body fat weight (r = 0.309, P = 0.01) and waist circumference (r = 0.386, P = 0.004). There was a positive correlation between TSH concentration and body weight (r = 0.227, P = 0.042) and body fat weight (r = 0.268, P = 0.038). After 6 months of obesity treatment, thyroid volume (P = 0.008) and TSH concentration (P = 0.006) decreased only in obese women who lost > 10% body weight. There was a positive correlation between the changes of thyroid volume and the change of body weight (r = 0.341, P = 0.009) and the change of body fat weight (r = 0.406, P = 0.013). CONCLUSIONS: Our study suggests that thyroid volume and function may vary in obese women in association with body weight and fat mass; > 10% weight loss may affect thyroid volume and function, which however, is clinically insignificant.     

In the absence of weight loss, exercise training does not improve adipokines or oxidative stress in overweight children

The aim of the present study was to examine the effect of exercise training on adipokines, inflammatory markers, and oxidative stress in overweight children. Nineteen overweight children were randomly assigned to an aerobic exercise training or sedentary control group for 8 weeks. Measurements included peak oxygen uptake (V o(2)max), body weight and composition, adipokines (C-reactive protein, interleukin 6, tumor necrosis factor alpha, adiponectin, leptin, and resistin), and oxidative stress (8-isoprostane). There were no differences between groups for change in body weight or composition over the 8 weeks. Exercise training improved V o(2)max (exercise group, 1.64 +/- 0.13 to 1.85 +/- 0.17L/min vs control group, 1.83 +/- 0.12 to 1.60 +/- 0.13 L/min, P < .05) but did not change any of the measured adipokines or the marker of systemic oxidative stress, 8-isoprostane. These data suggest that in the absence of weight loss, exercise training alone does not improve the adipokine profile or levels of oxidative stress in overweight children.     

Short-term weight cycling in aging female rats increases rate of weight gain but not body fat content

OBJECTIVE: To examine the effects of short-term repeated weight cycling (WC) above and below the baseline (BL) body weight (BW) on body weight regulation, feeding efficiency, and fat content in old female Wistar rats when dietary fat content was kept constant. DESIGN: Completely randomized. ANIMALS AND METHODS: Female Wistar rats, 11 months old at the beginning of the study, were randomly divided into six groups (12 per group) after a group of rats (BL) was sacrificed for baseline data collection: the high fat gain (HFG) group gained weight to 20% above the BL weight with a high fat diet (HF) and returned to BL level by food restriction (50% of ad-libitum amount) for five cycles; the high fat loss (HFL) group lost weight to 20% below the BL weight by food restriction (50% of ad-libitum amount) and regained to BL level by ad-libitum feeding for four cycles; the high fat ad-libitum (HFA) and low fat ad-libitum (LFA) groups were fed HF and low fat (LF) diet, respectively, ad-libitum for the entire study; the high fat restricted (HFR group) and low fat restricted rats (LFR group) were fed the HF and LF diet, respectively, in restricted amounts to maintain BW at BL level. RESULTS: A trend of increased rates of weight gain and feeding efficiencies from the first to last cycles for both WC groups was observed, and significant increases was observed between cycles 4 and 5. The rate of weight gain and feeding efficiency of HFL was significantly higher than that of the HFG group for all cycles (P<0. 05). The rates of weight loss were significantly decreasing with each successive cycle for HFG, but were unchanged for HFL. Percentage of body fat was not modified permanently from BL to sacrifice for both HFG and HFL groups. The body fat of HFA was higher than that of the other groups (P<0.01), while the body fat of LFA was significantly higher than that of the LFR, BL and HFL groups (P<0.01), but was similar to that of the HFG and HFR groups. The body fat of WC groups and HFR were similar to each other. The percentage of internal fat (retroperitoneal+omental) were similar for the WC groups. The percentage of internal fat of the HFG, HFR and LFA groups were similar, but were significantly higher than that of the BL and LFR groups (P<0.05). The percentage of internal fat of HFA was significantly higher than that of the rest of the groups (P<0.01). CONCLUSION: Short-term WC did not affect body fat content in these animals, but since weight gain became easier and weight loss became more difficult for animals in the HFG group, repeated WC may promote obesity in these rats.     

Prognostic impact of weight loss in 1-year survivors after transthoracic esophagectomy for cancer

Malnutrition is common 1 year after esophageal cancer surgery. However, the prognostic impact of this malnutrition on long-term outcome has been poorly reported. This study aims at determining the potential effect on disease-free survival (DFS) of weight loss observed at 1 year in disease-free survivors after curative esophageal resection. From a prospective single-institution database, 304 patients having undergone a transthoracic esophagectomy with two-field lymphadenectomy and gastric reconstruction between 1996 to 2008 were identified. Patients who died during the postoperative course (n= 24), patients who died within the first postoperative year (n= 12), patients who presented with an early recurrence within the first postoperative year (n= 20), and those who were lost to follow-up (n= 22) were excluded from the study, as well as those for whom the follow-up was shorter than 1 year (n= 21). The remaining 205 patients constituted a homogeneous group of 1-year disease-free survivors after full postoperative work-up and formed the material of the present study. Body weight (BW) values were collected before any treatment at the onset of symptoms (initial BW) and 1 year after esophagectomy. A 1-year weight loss (1-YWL) exceeding 10% of the initial BW defined an important malnutrition. Impact of the 1-YWL ≥ or <10% of the initial BW on DFS was investigated. Logistic regression was performed to identify factors affecting DFS. The mean initial BW was 69.1 ± 12 kg, corresponding to a mean body mass index (BMI) of 23.8 ± 3 kg/m(2) . Preoperatively, 32 (15%) patients were in the underweight category (BMI < 20 kg/m2), 110 (54%) were in normal (BMI = 20-24 kg/m2), and 63 (31%) were in the overweight category (BMI ≥ 25 kg/m2). Mean 1-year BW was 63.5 ± 12 kg. 1-YWL was <10% of the initial BW in 92 patients (45%) and ≥ 10% in 113 patients (55%). Accordingly, 5-year DFS rates were 66% (median: 80 months) and 48% (median: 51 months), respectively (P= 0.005). On multivariate analysis, only three independent variables affected the DFS significantly: clinical N stage (cN) status (P= 0.007; odds ratio: 1.99, 1.2-3.3), incomplete resection (P= 0.008, OR: 3.6, 1.3-9.3), and 1-YWL ≥ 10% (P= 0.004, OR: 2.1: 1.2-3.4). 1-YWL of or exceeding 10% of the initial BW in 1-year disease-free survivors has a negative prognostic impact on DFS after esophagectomy for cancer. This information offers another view on the objectives of the perioperative nutritional care of these patients. Special vigilance program on the nutritional status in post-esophagectomy patients should be the rule.     

Estradiol increases body weight loss and gut-peptide satiation after Roux-en-Y gastric bypass in ovariectomized rats

Despite the fact that ～85% of bariatric operations are performed in women, the effects of the reproductive axis function on outcome of bariatric surgery remain to be determined. Here we developed the first published model of Roux-en-Y gastric bypass (RYGB) in female rats. We show in ovariectomized rats receiving estradiol or control treatment that (1) RYGB-induced body weight loss and (2) the satiating efficacy of endogenous glucagon-like peptide-1 and cholecystokinin satiation were significantly increased in estradiol-treated rats. These data are relevant to the care of obese women, in particular perimenopausal women, undergoing bariatric surgery.     

Determinants of life expectancy in medullary thyroid cancer: age does not matter

OBJECTIVE: In medullary thyroid cancer (MTC) age is considered an important prognostic factor but survival has never been properly adjusted for baseline mortality in the general population. We aimed to identify prognostic factors by analysing patients with MTC regarding life expectancy. DESIGN: We described a retrospective cohort study with a median follow-up of 8 years (range 1-35 years). PATIENTS: We included 120 consecutive patients of whom 66 (55%) had sporadic MTC. Male/female ratio was 1 : 1; median age was 45 years (range 3-83 years). MEASUREMENTS: Measurements were overall and disease-specific survival and life expectancy expressed as survival adjusted for baseline mortality rate in the general population. RESULTS: Overall and disease-specific 10-year survival was 65% and 73%, respectively. After 10 years, 29% of patients were biochemically and 63% clinically cured. Median overall life expectancy was 0.58 (95%CI 0.37-0.80). Detectable recurrence occurred in 60 patients after a median of 36 months (range 5-518 months). On multivariate regression analysis only stage of disease and extrathyroidal extension predicted recurrence-free life expectancy. Extrathyroidal extension was the only independent predictor of overall life expectancy. Persistent biochemical MTC did not independently affect life expectancy but calcitonin doubling time of less than one year indicated worse prognosis. Patients without detectable recurrences after initial treatment had a life expectancy similar to the general population. CONCLUSIONS: In MTC patients, extrathyroidal extension and stage at diagnosis are the only independent predictors of (recurrence-free) life expectancy. Patients diagnosed in an early stage of disease and patients without detectable recurrence have favourable life expectancy independently of biochemical cure.     

Non‐irradiated female survivors of childhood acute lymphoblastic leukaemia are at risk of long‐term increases in weight and body mass index

We report long‐term, including final height, auxological data from our retrospective study of non‐irradiated survivors of childhood acute lymphoblastic leukaemia (ALL). Body mass index (BMI) standard deviation score (SDS) increases in females, due to increased weight‐SDS, persisted to final height, with probable adverse long‐term health outcomes. In contrast, males demonstrated increased BMI‐SDS in follow‐up, due to reduced height‐SDS, not increased weight‐SDS, but such changes had resolved by final height. Childhood ALL survivors, particularly females, are therefore at potential increased risk of developing the metabolic syndrome during follow‐up. We recommend that strategies to minimize weight gain should be implemented during ALL treatment.     

Knee strength maintained despite loss of lean body mass during weight loss in older obese adults with knee osteoarthritis

BACKGROUND: The effects of weight loss on muscle function in older adults have not been well studied. This study determined the effects of a 6-month weight-loss intervention on muscle strength and quality in older obese adults with knee osteoarthritis. METHODS: Participants were randomized to a weight loss (WL) (n = 44, 70 +/- 6 years) or weight stable (WS) (n = 43, 69 +/- 6 years) group. The WL intervention consisted of weekly educational meetings, a meal replacement diet, and a three-session-per-week structured exercise program to achieve 10%-12% weight loss. The WS intervention included bimonthly group meetings and newsletters. Body composition and knee extensor strength were measured at baseline and after intervention. RESULTS: The WL group decreased body weight, lean body mass, fat mass, and percent body fat (p <.001 for all). Concentric extension strength increased 25% in WL (p >.05), whereas eccentric extension decreased 6% in WS (p =.028). Concentric muscle quality (strength per kg body weight or lean body mass) increased in WL (p <.05), whereas eccentric muscle quality decreased in WS (p <.05). Changes in lean body mass and fat mass were inversely associated with changes in most muscle strength and quality measures (p <.05). Men and women did not differ in response to the intervention in knee strength outcomes. CONCLUSIONS: Hypocaloric dieting in combination with exercise training had beneficial effects on muscle strength/quality, despite loss of lean body mass in this sample of older men and women. Greater fat loss was associated with greater gains in muscle strength and quality. More studies are needed regarding the mechanisms by which loss of fat mass increases muscle strength and quality.