Sustained Decrease In Body Weight Research Articles

Cardiovascular risk reduction following metabolic and bariatric surgery.

Cardiovascular disease (CVD) is the world’s leading cause of mortality and obesity is a well-recognized risk factor of CVD. Early detection and management of CVD is critical to reduce CVD risk. Especially in patients suffering from obesity with obesity-related CVD risk factors such as hypertension (HTN), dyslipidemia, and diabetes mellitus (DM). A substantial and sustained decrease in body weight after metabolic and bariatric surgery is associated with a significant reduction of cardiovascular risk factors. This article reviews CVD risk models, mechanisms of CVD risk associated with obesity, and overall CVD risk reduction between different metabolic and bariatric procedures.

Protective Potential and Antidiabetic Activity of Bilberry Leaves in Zucker Rats

Objective: The protective potential of Bilberry Leaves Extract (BLE) was studied in the experiment on male diabetic obese Zucker rats (ZDF) rats (Crl:ZUC-Lepr(fa)) with liver metabolism disorders and hyperglycemia. Methods: Animals were fed with or without BLE (2 g/kg b.w.) orally via a gastric tube for 28 days. At the end of the experiment, biochemical and morphological indices were studied. Results: Daily intake of BLE in obese ZDF rats produced a marked and sustained decrease in body weight without an increase in food intake in comparison with untreated obese rats. By the end of the study, fasting blood glucose for rats receiving BLE was significantly lower than in control group (P<0.05). The serum levels of aspartate aminotransferase and alkaline phosphatase, biomarkers of liver damage, were significantly (P<0.05) lower in BLE group compared to the obese control animals. There were also reductions (P<0.05) in total cholesterol and high-density lipoproteins levels associated with BLE treatments. BLE administration to obese rats significantly reduced serum urea levels compared to the untreated obese rats. The results also showed a decrease in liver/body weight ratio which is undoubtedly a positive effect together with a general reduction in body weight in BLE treated animals. Conclusion: These data suggest that BLE inhibited the development of hyperglycemia, improved lipid metabolism, and influenced positively on some integral indices and a histological picture in the target organs of obese ZDF rats.

Effect on Liver Enzymes of Biliopancreatic Diversion: 4 Years of Follow-Up

Background: Elevated serum aminotransferase levels are commonly associated with obesity and with a progression to chronic liver disease. Bariatric surgery is the most effective strategy to achieve weight loss. Methods: We conducted the present study with the aim of evaluating the influence of biliopancreatic diversion (BPD) on liver enzymes levels during 4 years in morbid obese patients with normal aminotransferase (n = 65) and in morbid obese patients with high aminotransferase basal levels (n = 50). Results: A decrease in alanine aminotransferase and aspartate aminotransferase activities was significant after biliopancreatic diversion. The basal percentage of high aminotransferase levels and percentage of ratio ALT/AST <1 also decreased significantly at 1-, 2-, 3- and 4-years of follow-up in both groups. ALT (52 to 20%), AST (42 to 10%) and ALT/AST (80 to 22%) in patients with normal aminotransferase. ALT (82 to 20%), AST (70 to 6%) and ALT/AST (90 to 20%) in patients with elevated transaminase basal levels. Bariatric surgery was associated with a significant and sustained decrease in body weight in both groups. Serum trasnaminases level changes were positively correlated to body weight changes during follow-up. Conclusion: BPD is an effective method of achieving sustainable weight loss and reduced aminotransferase levels and enzyme ratios of liver damage.

Significant Association of Nightly Nasal Continuous Positive Airway Pressure Using Time with Weight Change in Japanese Patients with Obstructive Sleep Apnea-Hypopnea Syndrome

Background: Obstructive sleep apnea syndrome (OSAS) is one of the representative sleep disorders believed to be associated with metabolic syndrome. Nasal continuous positive airway pressure (nCPAP) ventilation is the first choice therapy for OSAS, which has been reported to cause an improvement in body fat mass, hepatocellular damage and hypertension. Study Objectives: We evaluated whether the changes in the body weight observed in patients with OSAS may have potential associations with the sleep time during which the patients are under nCPAP. Method: A total of 194 patients (148 obese and 46 non-obese) in whom nCPAP use was present for more than 70% of the nights were enrolled in this study. Using the electronic records of the night use time for CPAP devices, we examined whether the habitual sleep time during nCPAP is associated with changes in body weight. Results: In the non-obese OSAS group, the patients with night time use of nCPAP devices for 6 to 7 hours showed the greatest and the most sustained decrease in body weight. In the obese patients with OSAS, on the other hand, a U-shaped relationship has been demonstrated between a percent weight gain over 9 years and a minimal weight gain in patients with habitual sleep for 5 to 6 hours. Conclusions: These results suggest that changes in body weight in patients with OSAS are associated with habitual sleep time.

Duodenal nutrient exclusion improves metabolic syndrome and stimulates villus hyperplasia

ObjectiveSurgical interventions that prevent nutrient exposure to the duodenum are among the most successful treatments for obesity and diabetes. However, these interventions are highly invasive, irreversible and often carry significant...

Body fat and body weight reduction following hypothalamic deep brain stimulation in monkeys: an intraventricular approach

The authors proposed an intraventricular 'floating' electrode inserted in the third ventricle (V3) adjacent to the ventromedian hypothalamus (VMH) in a freely moving Macaca fascicularis to modulate food intake (FI), body fat (BF), body weight (BW) and body mass index (BMI), as a potential treatment of obesity. Five adult Macaca fascicularis monkeys were implanted stereotactically in the V3 contiguous to the VMH with one deep brain stimulation (DBS) electrode. The study was divided in two phases: (a) acute 24 h-fasting trials: different electrical stimulation parameters were applied to a fasting primate to determine the best combination in reducing FI; and (b) chronic 8-week stimulation trials: three cycles of intraventricular-VMH DBS lasting 8-10 weeks were performed at 130 Hz, 80 Hz (most effective frequency reducing FI) and 30 Hz, respectively. BMI, BW, BF content, skinfolds and hormones were measured during baseline and at the end of each session of stimulation. Acute 24 h-fasting trials: there was a decrease in FI in all subjects at 80 Hz, (11-19%, mean 15%). Chronic 8-week stimulation trials: a significant decrease in BW and BMI was observed in three out of four monkeys at 80 Hz (mean 8 ± 4.4%). Subcutaneous skinfolds were reduced in all four subjects at 80 Hz and slightly increased at 130 Hz. The sham monkey remained stable. No significant adverse effects were recorded. The stimulation of the VMH region through an intraventricular approach might acutely modulate FI and induce a sustained decrease in BW and fat mass in normal non-human primate.

The Effects of Rimonabant on Brown Adipose Tissue in Rat: Implications for Energy Expenditure

The cannabinoid CB1 receptor antagonist rimonabant (SR 141716) produces a sustained decrease in body weight on a background of a transient reduction in food intake. An increase in energy expenditure has been implicated, possibly mediated via peripheral endocannabinoid system; however, the role of the central endocannabinoid system is unclear. The present study investigates this role. Rimonabant (10 mg/kg IP) was administered for 21 days to rats surgically implanted with biotelemetry devices to measure temperature in the interscapular brown adipose tissue (BAT). BAT temperature as a putative measure of thermogenesis in the BAT, physical activity, body weight, food intake, as well as changes in UCP1 messenger RNA (mRNA) and protein were measured. In addition, role of the CNS in mediating these actions of rimonabant was determined in rats where the BAT was sympathetically denervated. As expected, chronic administration of rimonabant significantly reduced body weight for the entire treatment period despite only a transient decrease in food intake. There was a profound increase in BAT temperature, particularly during the dark phase of each circadian cycle throughout the treatment period. A corresponding increase in uncoupling protein (UCP1) was also observed following chronic rimonabant treatment. The rimonabant-induced elevation in BAT temperature and decrease in body weight were significantly attenuated following denervation, indicating an involvement of the CNS. These findings suggest that the long-term weight loss associated with rimonabant treatment is due at least in part to an elevation in energy expenditure, represented here by elevated temperature recorded in the BAT, which is mediated primarily by the central endocannabinoid system.

Blockade of cannabinoid CB1 receptors improves renal function, metabolic profile, and increased survival of obese Zucker rats

Obesity is a major risk factor in the development of chronic renal failure. Rimonabant, a cannabinoid CB1 receptor antagonist, improves body weight and metabolic disorders; however, its effect on mortality and chronic renal failure associated with obesity is unknown. Obese Zucker rats received either rimonabant or vehicle for 12 months and were compared to a pair-fed but untreated group of obese rats. Mortality in the obese rats was significantly reduced by rimonabant along with a sustained decrease in body weight, transient reduction in food intake, and an increase in plasma adiponectin. This was associated with significant reduction in plasma total cholesterol, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio, triglycerides, glucose, norepinephrine, plasminogen activator inhibitor 1, and preservation of pancreatic weight and beta-cell mass index. The cannabinoid antagonist attenuated the increase in proteinuria, urinary N-acetylglucosaminidase excretion, plasma creatinine, and urea nitrogen levels while improving creatinine clearance. Renal hypertrophy along with glomerular and tubulointerstitial lesions were reduced by rimonabant. Although the drug did not modify hemodynamics, it normalized the pressor response to angiotensin II. Our study suggests that in a rat model of chronic renal failure due to obesity, rimonabant preserves renal function and increases survival.

The effect of the cannabinoid receptor antagonist, rimonabant (SR 141716) on energy expenditure.

The cannabinoid CB1 receptor antagonist rimonabant (SR 141716) produces a sustained decrease in body weight on a background of a transient reduction in food intake. An increase in energy expenditure has been implicated, possibly mediated via the peripheral endocannabinoid system; however, the role of the central endocannabinoid system is unclear. In this study, rimonabant (10 mg/kg i.p.) was administered for 21 days to rats surgically implanted with biotelemetry devices to measure thermogenic activity in the interscapular brown adipose tissue (IBAT). Thermogenesis, physical activity, body weight, and food intake were measured. In addition, the role of the CNS in mediating these actions of rimonabant was determined by cutting the sympathetic nerves projecting to the IBAT. As expected chronic administration of rimonabant significantly reduced body weight for the entire treatment period despite only a transient decrease in food intake. There was a profound increase in thermogenesis, particularly during the dark phase of each circadian cycle of IBAT temperature throughout the treatment period. The rimonabant-induced elevation in IBAT temperature and decrease in body weight were significantly attenuated following denervation, indicating an involvement of the CNS. These findings show that the long term weight loss associated with rimonabant treatment is likely due to an elevation in thermogenesis mediated primarily by the central endocannabinoid system.

The anti‐obesity effect of rimonabant is associated with an improved serum lipid profile

We investigated the effects of chronic treatment with the CB1 receptor antagonist rimonabant (10 mg/kg/day p.o. for 10 weeks) in mice with established obesity (5-month high-fat diet). Untreated obese mice showed a weight gain of 46% (45.0 +/- 0.6 g vs. 30.8 +/- 0.5 g) compared with age-matched animals fed a standard diet. Rimonabant treatment, commencing after 5-month high-fat diet, produced a marked and sustained decrease in body weight (34.5 +/- 0.8 g vs. 47.2 +/- 0.5 g in the high-fat vehicle group, p < 0.001). The anti-obesity effect of rimonabant was similar to that obtained by switching obese mice from high-fat diet to standard laboratory diet during 10 weeks (final weight 33.7 +/- 0.6 g) and was associated with only transient (14 days) reduction in energy intake. Serum leptin, insulin and glucose levels were markedly elevated in obese animals. Rimonabant treatment significantly reduced these elevations (leptin -81%, insulin -78%, glucose -67%, p < 0.001 in all cases vs. high-fat vehicle group). In addition, rimonabant treatment modestly but significantly increased serum adiponectin levels (+18%, p < 0.05 vs. high-fat vehicle group). Obese mice demonstrated abnormal serum lipid profiles. Although rimonabant did not modify high-density lipoprotein cholesterol (HDLc) and had modest effects on total cholesterol, it significantly reduced triglycerides and low-density lipoprotein cholesterol (LDLc) and, notably, increased the HDLc/LDLc ratio (12.4 +/- 0.8 vs. 7.9 +/- 0.2 in high-fat vehicle group, p < 0.001). Therefore, in a model of established obesity, chronic rimonabant treatment produces a marked and sustained decrease in body weight (equivalent to that achieved by dietary change) which is associated with favourable modifications in serum biochemical and lipid profiles.

Activation of the sympathetic nervous system by galanin-like peptide--a possible link between leptin and metabolism.

The effects of leptin upon body weight (BW) cannot be explained by its anorectic actions alone. Part of the metabolic changes elicited by leptin includes sympathetic nervous system activation leading to increased energy expenditure. Galanin-like peptide (GALP), a recently described hypothalamic neuropeptide, is up-regulated by leptin and has anorectic effects in the mouse. We postulated that GALP mediates effects of leptin upon metabolism. To test this hypothesis, we administered GALP centrally to the leptin-deficient ob/ob mouse. Acutely, GALP induced a decrease in food intake and BW, both of which remained significant relative to controls for 4 d. Chronic GALP administration resulted in a sustained decrease in BW and an increase in core body temperature, despite significant recovery of food intake. In a pair-fed model, chronic GALP treatment resulted in a greater decrease in BW than that seen in controls. Furthermore, GALP treatment resulted in increased body temperature and uncoupling protein 1 mRNA and protein in brown adipose tissue compared with controls. The expression of pro-opiomelanocortin (POMC) mRNA in the arcuate nucleus was decreased after chronic GALP treatment. These observations suggest that leptin's activation of the sympathetic nervous system, and ultimately thermogenesis, may be partially mediated by GALP through a melanocortin-independent mechanism.

Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist

Melanin concentrating hormone (MCH) is an orexigenic hypothalamic neuropeptide, which plays an important role in the complex regulation of energy balance and body weight. Here we show that SNAP-7941, a selective, high-affinity MCH1 receptor (MCH1-R) antagonist, inhibited food intake stimulated by central administration of MCH, reduced consumption of palatable food, and, after chronic administration to rats with diet-induced obesity, resulted in a marked, sustained decrease in body weight. In addition, after mapping the binding sites for [(3)H]SNAP-7941 in rat brain, we evaluated its effects in a series of behavioral models. SNAP-7941 produced effects similar to clinically used antidepressants and anxiolytics in three animal models of depression/anxiety: the rat forced-swim test, rat social interaction and guinea pig maternal-separation vocalization tests. Given these observations, an MCH1-R antagonist may be useful not only in the management of obesity but also as a treatment for depression and/or anxiety.

Tiopronin protects against the nephrotoxicity of cisplatin in the rat.

1. Tiopronin (N-(2-mercaptopropionyl)-glycine) is a drug with a free thiol (sulphydryl) group that is used clinically. We have reported previously that tiopronin protects rat kidney slices in vitro from the nephrotoxic effects of cisplatin and does not reduce the antitumour activity of cisplatin. Tiopronin has been investigated therefore for its protective effects in rats in vivo. 2. The extent of kidney damage was studied 5 days after the administration of cisplatin. A single injection (i.p.) of cisplatin (6 mg/kg; 20 micromol/kg) to female Wistar albino rats caused a sustained decrease in body weight and, after 5 days, plasma urea, creatinine and kidney weight were increased. Tiopronin (2.5 mmol/kg, p.o.) ameliorated cisplatin nephrotoxicity when given 1 h before cisplatin. Tiopronin provided marked protection against cisplatin-induced increases in urea (from 237+/-19 mg to 48+/-23 mg/100 ml; control: 17+/-1) and creatinine (from 6.5+/-0.5 to 1.7+/-0.5 mg/100 ml control: 1.0+/-0.1). Tiopronin did not, prevent the body weight loss caused by cisplatin. In addition, an intraperitoneal dose (1 mmol/kg) of tiopronin afforded similar protection to that of an oral dose. Rats that received an i.p. mixture of cisplatin (6 mg/kg) and tiopronin (65 mg/kg) displayed generally less toxicity, as indicated by a small fall in body weight and smaller increases in urea and creatinine and kidney weight. 3. The results show that tiopronin protects against cisplatin-induced nephrotoxicity. Oral administration of tiopronin may be a clinically useful way to prevent cisplatin nephrotoxicity.

Metabolic abnormalities linked to obesity: Effects of dexfenfluramine in the corpulent rat

The JCR:LA-corpulent rat is a useful experimental model for the obese-diabetic-dyslipidemic syndrome that mimics the human condition and exhibits spontaneous development of atherosclerosis and myocardial lesions. A 30-day treatment of 6-month-old rats with dexfenfluramine 1, 2.5, and 5 mg per kilogram decreased body weight through loss of adipose tissue mass. The effect is caused primarily by the ability of dexfenfluramine to reduce food intake. The maximum depression of food intake and greatest weight loss is seen during the first 10 days of treatment in this experimental model; thereafter, body weight stabilizes. However, during this period, there is a marked decrease in serum concentrations of triglycerides, cholesterol, and insulin. Corpulent male rats were also treated from 6 to 37 weeks of age with dexfenfluramine 2.5 mg/kg. This also produces a sustained decrease in body weight and a decrease in circulating insulin concentrations. Preliminary evidence demonstrates a substantial decrease in the incidence of necrotic myocardial lesions produced by ischemic events. This study establishes that dexfenfluramine treatment can decrease the severity of associated risk factors for cardiovascular disease, namely obesity, diabetes, and dyslipidemias. Furthermore, we report the first evidence that long-term treatment with dexfenfluramine can largely prevent the occurrence of myocardial lesions and end-stage cardiovascular disease in this animal model prone to atherosclerosis.

Sustained decreases in weight and serum insulin, glucose, triacylglycerol and cholesterol in JCR:LA-corpulent rats treated with D-fenfluramine.

1. The effects of D-fenfluramine were studied in the JCR:LA-corpulent rat that is grossly obese, hyperphagic, hyperlipidaemic, hyperinsulinaemic and atherosclerosis-prone. 2. Daily doses of 1, 2.5 and 5 mg kg-1 of D-fenfluramine produced sustained decreases in body weight and food intake over a period of 30 days in 6 month old female rats fed ad libitum. This was accompanied by decreases in the circulating concentrations of glucose, triacylglycerol, free cholesterol and insulin. 3. Food restriction imposed by meal feeding also decreased circulating glucose, triacylglycerols, cholesterol and insulin and diminished the effect of D-fenfluramine on these parameters in male and female rats. 4. Addition of D-fenfluramine to drinking water to give a dose of about 0.25 mg kg-1 daily produced a sustained decrease in body weight and food intake of male and female rats over a nine week period. 5. The results show that the JCR:LA-corpulent rat is very sensitive to the pharmacological effects of D-fenfluramine. These rats should provide an appropriate animal model for determining the mechanisms of action of this anti-obesity agent and whether apparently beneficial changes in metabolism translate into long-term protection against premature atherosclerosis.

Prevention of adjuvant‐induced cachexia in rats by cyclosporin A

The changes in food intake and biochemistry following Freund's adjuvant (AJ)-induced inflammation in rats were investigated. Injection of AJ into rats resulted in a transient anorexia but a sustained decrease in body weight. Within 14 days, body weight decreased by 12% (P less than 0.05) and adipose tissue (retroperitoneal fat pads) decreased by more than 50%. Biochemical changes seen in association with the AJ-induced wasting included decreased plasma concentrations of triglyceride and cholesterol. Injection of cyclosporin-A (CS) (20 mg/kg) with the AJ decreased the anorexia, prevented the sustained loss of body weight and adipose tissue and reversed the effects on plasma triglyceride and cholesterol concentrations. Insulin concentrations were not significantly affected by the AJ or AJ/CS treatments. Peritoneal macrophages from AJ-treated rats produced 3-fold more tumour necrosis factor-alpha (cachectin) than control rats. This effect was not observed in rats treated with AJ plus CS. The results are consistent with CS preventing the release of cytokines which have anorectic and catabolic actions (IL-1, TNF), although there is also the possibility that CS has effects involving endocrine mechanisms.

Effects of a brain-enhanced chemical delivery system for estradiol on body weight and food intake in intact and ovariectomized rats.

Studies were undertaken to determine the effects on body weight of a brain-enhanced chemical delivery system for estradiol. This estradiol-chemical delivery system (E2-CDS) has a long half-life in the brain, where it slowly releases estradiol but is quickly cleared from peripheral tissues. We administered, by a single iv injection, E2-CDS (0.2, 1.0, or 5.0 mg/kg), equimolar doses of another 17-hydroxy-substituted estrogen, estradiol valerate (E2-VAL), or the dimethyl sulfoxide (DMSO) vehicle to female rats. Daily food intake and body weight was determined for 24 days thereafter. E2-CDS caused an initial dose-dependent suppression in body weight for up to 8 days and a suppression in food intake for up to 4 days. In response to E2-VAL, the initial declines in body weight and food intake were lower in magnitude, were shorter in duration, and showed no dose dependency. Following this period of weight loss, E2-CDS-treated rats gained weight at a rate greater than that of the DMSO controls, and at the 0.2- and 1.0-mg/kg doses, body weights achieved were greater than control levels. To determine the role of the ovaries on this biphasic response to E2-CDS, long-term ovariectomized rats were treated with E2-CDS (1.0 mg/kg) or the vehicle and parameters of body weight regulation were determined for 25 days. Ovariectomized rats responded to E2-CDS with a prompt and sustained decrease in body weight which did not recover over the 25-day course of the study. The body-weight loss in ovariectomized rats was associated with a marked reduction in food intake for 8 days.(ABSTRACT TRUNCATED AT 250 WORDS)

The Long Term Effect of Estrogen Administration on the Metabolism of Male Rat Bone

Hundred and fifty-gram male rats were divided into four groups with the first containing intact controls, the second intact animals treated with 400 μg per 100 g body wt of 17-β-estradiol twice a week. The animals in the third group were castrated and those in the fourth were castrated and treated with the same dosage of estrogen. Animals were sacrificed at varying periods of time from one to 12 months. Estrogen administration caused a sustained decrease in body weight in the intact animal but did not change the body weight in castrated animals. Estrogen had no effect on either serum calcium or serum phosphorus. Estrogen administration to the intact animal caused a small but significant increase in ash content of bone. Castration caused a small decrease in this value which was still present at 12 months and estrogen administration returned the value to normal. Estrogen administration caused a decrease in total hydroxyproline content of bones of intact animals. Castration did not alter this value but estrogen administration to the castrated animal decreased the bone hydroxyproline content. Hydroxyproline incorporation rates were decreased in bones of both the intact and castrated animals. Castration did not alter the total hexosamine content of bones but estrogen administration to both the intact and castrated animals caused an increase in bone hexosamine content. Estrogen administration caused a decrease in the synthesis rate of proteoglycans in bones of both the intact and castrated animals. Estrogen administration caused a decrease in the uptake of radioactive calcium into bones of both the intact and castrated animals. There was no significant effect of estrogen on collagenolytic activity in male rat bone. It is concluded that estrogen administration to the male rat, causes changes which are different from those found in the female. There appeared to be no change in serum calcium or phosphorus values. A decreased synthesis of bone matrix and decreased uptake of radioactive calcium brought about no measurable change in the resorption of bone matrix.

ÉTUDE BIOCHIMIQUE DE LA MÉTAMORPHOSE DE TRIBOLIUM CONFUSUM DUVAL (COLÉOPTÈRE: TÉNÉBRIONIDAE): I. VARIATIONS DU POIDS CORPOREL, DE L'HUMIDITÉ, DE LA MATIÈRE SÈCHE ET DES CENDRES TOTALES

The variations in the total body weight, water content, dry weight, and total ash of Tribolium confusum during metamorphosis are reported. A drop in total body weight before the insect enters pupation is observed. The pupal stage shows a moderate but sustained decrease in body weight followed by a further large one at emergence. Though the water content falls during the prepupal stage and at the emergence, there is a moderate increase in the water content during the pupal stage. These changes show that the pupae utilize the reserves accumulated during the larval stage. Variations in both dry weight and total body weight are similar. A study of simple correlation of these variables is discussed. The elimination in the prepupal stage of a large amount of the inorganic constituents (ash) is noticed. During the pupal stage, total ash remains constant while at emergence, there is a slight fall.