Synthesis of Capsaicin Glycosides and 8-Nordihydrocapsaicin Glycosides as Potential Weight-Loss Formulations

The enzymatic synthesis of capsaicin glycosides and 8-nordihydrocapsaicin glycosides was investigated using almond β-glucosidase and cyclodextrin glucanotransferase (CGTase). Capsaicin and 8-nordihydrocapsaicin were converted into their β-glucoside and β-maltooligosaccharide (amylose conjugate), i.e. β-maltoside and β-maltotrioside, by sequencial glycosylation with almond β-glucosidase and CGTase. The β-glucoside and β-maltoside of capsaicin and β-glucoside of 8-nordihydrocapsaicin showed inhibitory effects on high-fat-diet-induced elevations in body weight of mice.

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High-fat diet induces site-specific unresponsiveness to LPS-stimulated STAT3 activation in the hypothalamus

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00147.2013 ◽

2014 ◽

Vol 306 (1) ◽

pp. R34-R44 ◽

Cited By ~ 7

Author(s):

Beatriz de Carvalho Borges ◽

Rodrigo Rorato ◽

Ernane Torres Uchoa ◽

Paula Marangon ◽

Glauber S. F. da Silva ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Food Intake ◽

Energy Expenditure ◽

Brain Stem ◽

High Fat Diet ◽

Control Diet ◽

Body Weight Loss ◽

Hypothalamic Nucleus ◽

High Fat

Hypophagia induced by inflammation is associated with Janus kinase (JAK)-2/signal transducer and activator of transcription (STAT) 3 signaling pathway, and leptin-mediated hypophagia is also mediated by JAK2-STAT3 pathway. We have previously reported that lipopolysaccharide (LPS) did not reduce food intake in leptin-resistant high-fat diet (HFD) rats but maintained body weight loss. We investigated whether changes in p-STAT3 expression in the hypothalamus and brain stem could account for the desensitization of hypophagia in HFD animals after a low LPS dose (100 μg/kg). Wistar rats fed standard diet (3.95 kcal/g) or HFD (6.3 kcal/g) for 8 wk were assigned into control diet-saline, control diet-LPS, HFD-saline, and HFD-LPS groups. LPS reduced feeding in the control diet but not HFD. This group showed no p-STAT3 expression in the paraventricular nucleus (PVN) and ventromedial hypothalamic nucleus (VMH), but sustained, though lower than control, p-STAT3 in the nucleus of the solitary tract (NTS) and raphe pallidus (RPa). LPS decreased body weight in HFD rats and increased Fos expression in the NTS. LPS increased body temperature, oxygen consumption, and energy expenditure in both control diet and HFD rats, and this response was more pronounced in HFD-LPS group. Brown adipose tissue (BAT) thermogenesis and increased energy expenditure seem to contribute to body weight loss in HFD-LPS. This response might be related with increased brain stem activation. In conclusion, LPS activates STAT3-mediated pathway in the hypothalamus and brain stem, leading to hypophagia, however, LPS effects on food intake, but not body weight loss, are abolished by leptin resistance induced by HFD. The preserved STAT3 phosphorylation in the brain stem suggests that unresponsiveness to LPS on STAT3 activation under HFD might be selective to the hypothalamus.

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Macronutrient balances and obesity: the role of diet and physical activity

Public Health Nutrition ◽

10.1017/s1368980099000464 ◽

1999 ◽

Vol 2 (3a) ◽

pp. 341-347 ◽

Cited By ~ 51

Author(s):

Arne Astrup

Keyword(s):

Physical Activity ◽

Weight Loss ◽

Body Weight ◽

Weight Gain ◽

Physical Fitness ◽

Dietary Fat ◽

High Fat Diet ◽

Fat Oxidation ◽

Fat Content ◽

High Fat

AbstractObservational cross-sectional and longitudinal studies suggest that a high fat diet and physical inactivity are independent risk factors for weight gain and obesity. Mechanistic and intervention studies support that fat possesses a lower satiating power than carbohydrate and protein, and a diet low in fat therefore decreases energy intake. The effect of dietary fat on energy balance is enhanced in susceptible subjects, particularly in sedentary individuals with a genetic predisposition to obesity who consume a high fat diet.Dietary carbohydrate promotes its own oxidation by an insulin-mediated stimulation of glucose oxidation. In contrast, high fat meals do not increase fat oxidation acutely. A sedentary life-style and low physical fitness cause a low muscular fat oxidation capacity, and the consumption of a high fat diet by these individuals promotes fat storage in a synergistic fashion.Ad libitum low fat diets cause weight loss proportional to pre-treatment body weight in a dose-dependent way, i.e. weight loss is correlated positively to the reduction in dietary fat content. Increased physical activity prevents relapse after weight loss and studies have shown that those who keep up a higher level of physical activity are more successful in maintaining the reduced body weight. In conclusion, important interactions exist between genetic make up, dietary fat and physical fitness, so that a low fitness level and susceptible genes reduce muscular fat oxidation capacity which may decrease the tolerance of dietary fat. Increasing daily physical activity and reducing dietary fat content may be more effective when combined than when separate in preventing weight gain and obesity.

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O-B04 The effect of high fat diet and subsequent intentional weight loss on tumour burden in an animal model of spontaneous endometrial cancer

British Journal of Surgery ◽

10.1093/bjs/znab429.003 ◽

2021 ◽

Vol 108 (Supplement_9) ◽

Author(s):

Piriyah Sinclair ◽

Michael Wilkinson ◽

Emer Conroy ◽

Paul Downey ◽

William Gallagher ◽

...

Keyword(s):

Weight Loss ◽

Animal Model ◽

Body Weight ◽

Endometrial Cancer ◽

High Fat Diet ◽

Abdominal Fat ◽

High Fat ◽

Intentional Weight Loss ◽

Imaging Protocol ◽

Pet Ct

Abstract Background Obesity drives endometrial cancer (EC). Metabolic surgery (MS) induces sustained weight loss, reduces EC risk and has been shown to reverse histological changes of endometrial hyperplasia. One mechanism is increased GLP-1 post surgery. Few interventional studies have been conducted in the BDII/Han rat; an animal model of spontaneous EC. This study aimed to examine whether high fat diet (HFD) and weight gain, as well as subsequent intentional weight loss using Liraglutide (a GLP-1 receptor agonist) alters EC tumour biology and burden in the BDII/Han rat. A rat imaging protocol was validated to assess development and longitudinally track tumours. Methods An imaging protocol was developed and validated. 7 BDII/Han rats were fed normal chow (NC) and 8 weight-matched rats fed HFD from 3 months of age. Longitudinal PET-CT was conducted at 7, 9, 12 and 15 months. Abdominal visceral fat was analysed from L1-L5 on CT. Subsequently, an intervention study compared the 8 HFD-Control rats to 8 weight-matched HFD-fed rats treated with Liraglutide from 12-15 months. PET-CT was used to assess disease progression. Analysis of histological, immunohistochemical and transcriptomic parameters were used to compare cohorts. All rats were euthanased aged 15-months. Imaging was correlated with necropsy findings and histopathology. Results HFD rats had more abdominal fat on CT imaging (8.6cm3±0.7vs4.0cm3±0.6;p<0.0005) and 10% higher body-weight than NC rats (232.5g±4.9vs209.4g±2.0;p=0.001) at the study end. Histopathology demonstrated EC in 57%(n = 4) of NC and 50%(n = 4) of HFD rats. PET-CT was 87.5% sensitive and 86% specific. Liraglutide induced significant reduction in final body weight (208.3g±5.7vs232.5g±4.9;p=0.006) and abdominal fat on CT compared to controls (4.4cm3±0.4vs8.6cm3±0.7; p=0.0001). 2 tumours were identified in the Liraglutide group (25%) compared to 4 in the control group (50%). GLP-1 receptor expression was not detected in benign or malignant BDII/Han uterine tissue. Conclusions This study has established a safe, sensitive and specific imaging protocol for longitudinal assessment of EC progression in BDII/Han rats. The HFD intervention used did not accelerate EC burden. However, it did create an obese phenotype and gave new information on the pathological variations of EC in the BDII/Han rat. Intentional weight loss from Liraglutide halved EC burden compared to controls in this study. An absence of GLP-1R expression may suggest weight loss dependent mechanisms. This novel pilot study is a foundation for future studies assessing the effect of intentional weight loss using metabolic surgery in obesity-related cancer.

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A Low-Protein High-Fat Diet Leads to Loss of Body Weight and White Adipose Tissue Weight via Enhancing Energy Expenditure in Mice

Metabolites ◽

10.3390/metabo11050301 ◽

2021 ◽

Vol 11 (5) ◽

pp. 301

Author(s):

Yifeng Rang ◽

Sihui Ma ◽

Jiao Yang ◽

Huan Liu ◽

Katsuhiko Suzuki ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Adipose Tissue ◽

Energy Expenditure ◽

White Adipose Tissue ◽

High Fat Diet ◽

Acid Oxidation ◽

High Fat ◽

Plasma Biomarkers ◽

Low Protein

Obesity has become a worldwide health problem over the past three decades. During obesity, metabolic dysfunction of white adipose tissue (WAT) is a key factor increasing the risk of type 2 diabetes. A variety of diet approaches have been proposed for the prevention and treatment of obesity. The low-protein high-fat diet (LPHF) is a special kind of high-fat diet, characterized by the intake of a low amount of protein, while compared to typical high-fat diet, may induce weight loss and browning of WAT. Physical activity is another effective intervention to treat obesity by reducing WAT mass, inducing browning of WAT. In order to determine whether an LPHF, along with exercise enhanced body weight loss and body fat loss as well as the synergistic effect of an LPHF and exercise on energy expenditure in a mice model, we combined a 10-week LPHF with an 8-week forced treadmill training. Meanwhile, a traditional high-fat diet (HPHF) containing the same fat and relatively more protein was introduced as a comparison. In the current study, we further analyzed energy metabolism-related gene expression, plasma biomarkers, and related physiological changes. When comparing to HPHF, which induced a dramatic increase in body weight and WAT weight, the LPHF led to considerable loss of body weight and WAT, without muscle mass and strength decline, while it exhibited a risk of liver and pancreas damage. The mechanism underlying the LPHF-induced loss of body weight and WAT may be attributed to the synergistically upregulated expression of Ucp1 in WAT and Fgf21 in the liver, which may enhance energy expenditure. The 8-week training did not further enhance weight loss and increased plasma biomarkers of muscle damage when combined with LPHF. Furthermore, LPHF reduced the expression of fatty acid oxidation-related genes in adipose tissues, muscle tissues, and liver. Our results indicated that an LPHF has potential for obesity treatment, while the physiological condition should be monitored during application.

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Effect of repeated stress on body weight and body composition of rats fed low- and high-fat diets

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.275.6.r1928 ◽

1998 ◽

Vol 275 (6) ◽

pp. R1928-R1938 ◽

Cited By ~ 34

Author(s):

Ruth B. S. Harris ◽

Jun Zhou ◽

Bradley D. Youngblood ◽

Igor I. Rybkin ◽

Gennady N. Smagin ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Food Intake ◽

High Fat Diet ◽

Corn Oil ◽

Coconut Oil ◽

High Fat ◽

Adult Rats ◽

Reduced Body ◽

Fat Diets

Exposure to the moderate stressor of 3-h restraint for 3 consecutive days causes a temporary drop in food intake but a permanent reduction in body weight in adult rats. Young rats did not show the same response. Food intake of adult rats exposed to repeated restraint was significantly lower than that of controls for 4 days after the end of stress, and there was no rebound hyperphagia. Body weight remained significantly lower for at least 40 days after stress. When the rats were fed a high-fat diet of 80% chow and 20% vegetable shortening (48% kcal fat, 16% protein), lean body mass accounted for all of the weight loss in stressed rats. When the experiment was repeated with a purified high-fat diet containing corn oil and coconut oil as the source of fat (41% kcal fat, 16% protein), weight loss consisted of both lean and fat tissue. There were no sustained changes in single time point measures of corticosterone, insulin, or leptin that could account for the reduced body weight in these rats.

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Effect of Monoclonal Antibody Blockade of Long Fragment Neurotensin on Weight Loss, Behavior, and Metabolic Traits After High-Fat Diet Induced Obesity

Frontiers in Endocrinology ◽

10.3389/fendo.2021.739287 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zherui Wu ◽

Nicolas Stadler ◽

Amazigh Abbaci ◽

Jin Liu ◽

Agnès Boullier ◽

...

Keyword(s):

Monoclonal Antibody ◽

Weight Loss ◽

Body Weight ◽

Muscle Fiber ◽

High Fat Diet ◽

Public Health Problem ◽

Major Public Health Problem ◽

High Fat ◽

Fat Depots ◽

Fiber Size

BackgroundObesity is a major public health problem of our time as a risk factor for cardiometabolic disease and the available pharmacological tools needed to tackle the obesity pandemic are insufficient. Neurotensin (NTS) is a 13 amino acid peptide, which is derived from a larger precursor hormone called proneurotensin or Long Form NTS (LF NTS). NTS modulates neuro-transmitter release in the central system nervous, and facilitates intestinal fat absorption in the gastrointestinal tract. Mice lacking LF NTS are protected from high fat diet (HFD) induced obesity, hepatic steatosis and glucose intolerance. In humans, increased levels of LF NTS strongly and independently predict the development of obesity, diabetes mellitus, cardiovascular disease and mortality. With the perspective to develop therapeutic tools to neutralize LF NTS, we developed a monoclonal antibody, specifically inhibiting the function of the LF NTS (LF NTS mAb). This antibody was tested for the effects on body weight, metabolic parameters and behavior in mice made obese by high-fat diet.MethodsC57bl/6j mice were subjected to high-fat diet (HFD) until they reached an obesity state, then food was switched to chow. Mice were treated with either PBS (control therapy) or LF NTS mAb at the dose of 5 mg/kg once a week (i.v.). Mice weight, plasma biochemical analysis, fat and muscle size and distribution and behavioral tests were performed during the losing weight period and the stabilization period.ResultsObese mice treated with the LF NTS mAb lost weight significantly faster than the control treated group. LF NTS mAb treatment also resulted in smaller fat depots, increased fecal cholesterol excretion, reduced liver fat and larger muscle fiber size. Moreover, mice on active therapy were also less stressed, more curious and more active, providing a possible explanation to their weight loss.ConclusionOur results demonstrate that in mice subjected to HFD-induced obesity, a blockade of LF NTS with a monoclonal antibody results in reduced body weight, adipocyte volume and increased muscle fiber size, possibly explained by beneficial effects on behavior. The underlying mechanisms as well as any future role of LF NTS mAb as an anti-obesity agent warrants further studies.

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Calorie-Restricted Weight Loss Reverses High-Fat Diet-Induced Ghrelin Resistance, Which Contributes to Rebound Weight Gain in a Ghrelin-Dependent Manner

Endocrinology ◽

10.1210/en.2012-1421 ◽

2013 ◽

Vol 154 (2) ◽

pp. 709-717 ◽

Cited By ~ 44

Author(s):

Dana I. Briggs ◽

Sarah H. Lockie ◽

Qunli Wu ◽

Moyra B. Lemus ◽

Romana Stark ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Weight Gain ◽

High Fat Diet ◽

Chow Diet ◽

Dependent Manner ◽

High Fat ◽

Dietary Interventions ◽

Set Point ◽

Reduced Body

Twelve weeks of high-fat diet feeding causes ghrelin resistance in arcuate neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons. In the current study, we investigated whether diet-induced weight loss could restore NPY/AgRP neuronal responsiveness to ghrelin and whether ghrelin mediates rebound weight gain after calorie-restricted (CR) weight loss. Diet-induced obese (DIO) mice were allocated to one of two dietary interventions until they reached the weight of age-matched lean controls. DIO mice received chow diet ad libitum or chow diet with 40% CR. Chow-fed and high-fat–fed mice served as controls. Both dietary interventions normalized body weight, glucose tolerance, and plasma insulin. We show that diet-induced weight loss with CR increases total plasma ghrelin, restores ghrelin sensitivity, and increases hypothalamic NPY and AgRP mRNA expression. We propose that long-term DIO creates a higher body weight set-point and that weight loss induced by CR, as seen in the high-fat CR group, provokes the brain to protect the new higher set-point. This adaptation to weight loss likely contributes to rebound weight gain by increasing peripheral ghrelin concentrations and restoring the function of ghrelin-responsive neuronal populations in the hypothalamic arcuate nucleus. Indeed, we also show that DIO ghrelin-knockout mice exhibit reduced body weight regain after CR weight loss compared with ghrelin wild-type mice, suggesting ghrelin mediates rebound weight gain after CR weight loss.

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Leptin prevents obesity induced by a high-fat diet after diet-induced weight loss in the marsupial S. crassicaudata

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00240.2003 ◽

2004 ◽

Vol 286 (4) ◽

pp. R734-R739 ◽

Cited By ~ 3

Author(s):

Gary A. Wittert ◽

Helen Turnbull ◽

Perdita Hope ◽

John E. Morley ◽

Michael Horowitz

Keyword(s):

Weight Loss ◽

Body Weight ◽

Food Intake ◽

Caloric Restriction ◽

High Fat Diet ◽

High Fat ◽

Fat Stores ◽

Ad Libitum ◽

Standard Laboratory Diet ◽

Ad Libitum Feeding

The aims of this study were to determine in the marsupial Sminthopsis crassicaudata, the effects of leptin on food intake, body weight, tail width (a reflection of fat stores), and leptin mRNA, after caloric restriction followed by refeeding ad libitum with either a standard or high-fat preferred diet. S. crassicaudata ( n = 32), were fed standard laboratory diet (LabD; 1.01 kcal/g, 20% fat) ad libitum for 3 days. On days 4-10, animals received LabD at 75% of basal intake and then ( days 11-25) were fed either LabD or a choice of LabD and mealworms (MW; 2.99 kcal/g, 30% fat); during this time, half the animals ( n = 8) in each group received either leptin (2.5 mg/kg) or PBS intraperitoneally two times daily. On day 26, animals were killed and fat was removed for assay of leptin mRNA. At baseline, body weight, tail width, and food intake were similar in each group. After caloric restriction, body weight ( P < 0.001) and tail width ( P < 0.001) decreased. On return to ad libitum feeding in the PBS-treated animals, body weight and tail width returned to baseline in the LabD-fed animals ( P < 0.001) and increased above baseline in the MW-fed animals ( P < 0.001). In the LabD groups, tail width ( P < 0.001) and body weight ( P < 0.001) decreased after leptin compared with PBS. In the MW groups, the increase in tail width ( P < 0.001) and body weight ( P = 0.001) were attenuated after leptin compared with PBS. The expression of leptin mRNA in groups fed MW were greater in PBS than in leptin-treated animals ( P < 0.05). Therefore, after diet-induced weight loss, leptin prevents a gain in fat mass in S. crassicaudata; this has potential implications for the therapeutic use of leptin.

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