scholarly journals Intestinal serine protease inhibition increases FGF21 and improves metabolism in obese mice

2019 ◽  
Vol 316 (5) ◽  
pp. G653-G667 ◽  
Author(s):  
Kamal Albarazanji ◽  
Matthew Jennis ◽  
Cassandre R. Cavanaugh ◽  
Wensheng Lang ◽  
Bhanu Singh ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Blood Glucose ◽  
Stress Response ◽  
Food Intake ◽  
Serine Protease ◽  
Plasma Levels ◽  
Metabolic Adaptation ◽  
Fibroblast Growth Factor 21 ◽  
Integrated Stress Response

Trypsin is the major serine protease responsible for intestinal protein digestion. An inhibitor, camostat (CS), reduced weight gain, hyperglycemia, and dyslipidemia in obese rats; however, the mechanisms for these are largely unknown. We reasoned that CS creates an apparent dietary protein restriction, which is known to increase hepatic fibroblast growth factor 21 (FGF21). Therefore, metabolic responses to CS and a gut-restricted CS metabolite, FOY-251, were measured in mice. Food intake, body weight, blood glucose, branched-chain amino acids (LC/MS), hormone levels (ELISA), liver pathology (histology), and transcriptional changes (qRT-PCR) were measured in ob/ob, lean and diet-induced obese (DIO) C57BL/6 mice. In ob/ob mice, CS in chow (9–69 mg/kg) or FOY-251 (46 mg/kg) reduced food intake and body weight gain to a similar extent as pair-fed mice. CS decreased blood glucose, liver weight, and lipidosis and increased FGF21 gene transcription and plasma levels. In lean mice, CS increased liver FGF21 mRNA and plasma levels. Relative to pair feeding, FOY-251 also increased plasma FGF21 and induced liver FGF21 and integrated stress response (ISR) transcription. In DIO mice, FOY-251 (100 mg/kg po) did not alter peak glucose levels but reduced the AUC of the glucose excursion in response to an oral glucose challenge. FOY-251 increased plasma FGF21 levels. In addition to previously reported satiety-dependent (cholecystokinin-mediated) actions, intestinal trypsin inhibition engages non-satiety-related pathways in both leptin-deficient and DIO mice. This novel mechanism improves metabolism by a liver-integrated stress response and increased FGF21 expression levels in mice. NEW & NOTEWORTHY Trypsin inhibitors, including plant-based consumer products, have long been associated with metabolic improvements. Studies in the 1980s and 1990s suggested this was due to satiety hormones and caloric wasting by loss of protein and fatty acids in feces. This work suggests an entirely new mechanism based on the lower amounts of digested protein available in the gut. This apparent protein reduction may cause beneficial metabolic adaptation by the intestinal-liver axis to perceived nutrient stress.

scholarly journals Vitamin D and Alcohol Differentially Effect Weight Gain in Older Female Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 541-541
Author(s):  
Brandon McGuire ◽  
Azra Dees ◽  
Anna Ogilvie ◽  
Sue Shapses
Keyword(s):  
Vitamin D ◽  
Body Composition ◽  
Body Weight ◽  
Weight Gain ◽  
Blood Glucose ◽  
Food Intake ◽  
Glucose Tolerance ◽  
Alcohol Intake ◽  
Caloric Intake ◽  
Increase Body Weight

Abstract Objectives Serum calcidiol is inversely associated with BMI in obese individuals and murine research has shown that vitamin D deficient diets (VDD) increase body weight. Alcohol intake doesn't necessarily increase body weight despite its caloric density but has been associated with VDD. The objective of this study was to determine the effect of vitamin D deficiency with or without alcohol on body weight, body composition, glucose tolerance, and energy expenditure in seven-month-old female mice. Methods Seven-month-old female retired breeder C57BL/6J mice (n = 40) were weight-matched and randomized to one of four diets: control (normal purified AIN-93 diet), vitamin D deficient (VDD, 0 intake of vitamin D), alcohol (Alc, 10% ethanol), or vitamin D deficient and alcohol (VDD + Alc). Mice were fed ad libitum for 8 weeks. Body weight and food intake were recorded weekly and body composition was measured at baseline and final time points using EchoMRI. Glucose tolerance and energy expenditure (EE) were assessed by an oral glucose tolerance test (OGTT) and Oxymax/CLAMS unit at week 8. Results Body weight at baseline was 27.4 ± 1.8 g and did not differ between groups. Mice drinking alcohol had a decreased food intake (p < 0.001). When liquid calories were accounted for, total caloric intake did not differ between groups. Weight gain throughout the study increased more in the VDD groups (p < 0.05). Increases in weight were 0.81 ± 2.9, 0.82 ± 2.0, 2.0 ± 1.7, and 3.6 ± 2.9 g, in the control, Alc, VDD, and VDD + Alc groups, respectively (p < 0.05). Lean body mass was also increased due to VDD (p < 0.05). The total fat mass did not differ significantly between groups, however, VDD groups gained more fat mass over time (p < 0.05). Two-way ANOVA showed an interaction between vitamin D and alcohol for EE (p < 0.05). Positive incremental area under the curve (IAUC) for blood glucose was decreased due to alcohol intake (p < 0.05). Conclusions In conclusion, alcohol intake decreased blood glucose and food intake, but there was no effect on total caloric intake, body weight or body composition. VDD led to greater increases in body weight and soft tissue compartments compared to other groups that were not explained by caloric intake or EE. Understanding mechanisms that are causing excess weight gain due to VDD is currently a focus in the lab. Funding Sources USDA-NIFA (NJAES).

Ventilation in newborn rats after gestation at simulated high altitude

1991 ◽  
Vol 70 (3) ◽  
pp. 1146-1151 ◽  
Author(s):  
R. D. Gleed ◽  
J. P. Mortola
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
High Altitude ◽  
Sea Level ◽  
Body Weight Gain ◽  
Female Rats ◽  
Metabolic Adaptation ◽  
Newborn Rats ◽  
Pregnant Rats

Pregnant rats were kept at a simulated altitude of 4,500 m (PO2 91 Torr) for the whole of gestation and returned to sea level 1 day after giving birth. During pregnancy, body weight gain and food intake were approximately 30% less than in controls at sea level. Measurements were made on the 1-day-old (HYPO) pups after a few hours at sea level. In normoxia, ventilation (VE) measured by flow plethysmography was more (+17%) and O2 consumption (VO2) measured by a manometric method was less (-19%) than in control (CONT) pups; in HYPO pups VE/VO2 was 44% greater than in CONT pups. In acute hyperoxia, VE/VO2 of HYPO and CONT pups decreased by a similar amount (15-20%), indicating some limitation in O2 availability for both groups of pups in normoxia. However, VE/VO2 of HYPO pups, even in hyperoxia, remained above (+34%) that of CONT pups. HYPO pups weighed slightly less than CONT pups, their lungs were hypoplastic, and their hearts were a larger fraction of body weight. An additional group of female rats was acclimatized (8 days) to high altitude before insemination. During pregnancy, body weight gain and food intake of these females were similar to those of pregnant rats at sea level. Measurements on the 1-day-old pups of this group were similar to those of HYPO pups. We conclude that newborn rats born after hypoxic gestation present metabolic adaptation (low VO2) and acclimatization (high VE/VO2), possibly because of hypoxemia. Maternal acclimatization before insemination substantially alters maternal growth in hypoxia but does not affect neonatal outcome.

Effect of Honey & Olive Oil Supplemented Bio-Yoghurt Feeding on Lipid Profile, Blood Glucose and Hematological Parameters in Rats

2019 ◽  
Vol 15 (2) ◽  
pp. 140-147
Author(s):  
Magdy M. Ismail ◽  
El-Tahra M. Ammar ◽  
Abd El-Wahab E. Khalil ◽  
Mohamed Z. Eid
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Blood Glucose ◽  
Olive Oil ◽  
Body Weight Gain ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol

Background and Objective: Yoghurt, especially bio-yoghurt has long been recognized as a product with many health benefits for consumers. Also, honey and olive oil have considerable nutritional and health effects. So, the effect of administration of yoghurt made using ABT culture and fortified with honey (2 and 6%), olive oil (1 and 4%) or honey + olive oil (2+1 and 6+4% respectively) on some biological and hematological properties of rats was investigated.Methods:The body weight gain, serum lipid level, blood glucose level, serum creatinine level, Glutamic Oxaloacetic Transaminase (GOT) activity, Glutamic Pyruvic Transaminase (GPT) activity, leukocytes and lymphocytes counts of rats were evaluated.Results:Blending of bio-yoghurt with rats' diet improved body weight gain. Concentrations of Total plasma Cholesterol (TC), High-Density Lipoprotein cholesterol (HDL), Low-Density Lipoprotein cholesterol (LDL), Very Low-Density Lipoprotein cholesterol (VLDL) and Triglycerides (TG) significantly lowered in plasma of rats fed bio-yoghurt. Levels of TC, LDL, VLDL, and TG also decreased in rat groups feed bio-yoghurt supplemented with honey and olive oil. LDL concentrations were reduced by 10.32, 18.51, 34.17, 22.48, 43.30% in plasma of rats fed classic starter yoghurt, ABT yoghurt, ABT yoghurt contained 6% honey, ABT yoghurt contained 4% olive oil and ABT yoghurt contained 6% honey + 4% olive oil respectively. The blood glucose, serum creatinine, GOT and GPT values of rats decreased while white blood cells and lymphocytes counts increased by feeding bioyoghurt contained honey and olive oil.Conclusion:The findings enhanced the multiple therapeutic effects of bio-yoghurt supplemented with honey and olive oil.

scholarly journals Ileal transposition helps to regulate plasma hepatokine levels in obese Zucker (Crl:ZUC(ORL)-Leprfa) rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dominika Stygar ◽  
Tomasz Sawczyn ◽  
Agnieszka Dulska ◽  
Elżbieta Chełmecka ◽  
Łukasz Mielańczyk ◽  
...  
Keyword(s):  
Body Weight ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
The Body ◽  
Retinol Binding Protein ◽  
Fibroblast Growth Factor 21 ◽  
Adult Males ◽  
Total Lipids ◽  
Ileal Transposition ◽  
Sham Surgery

AbstractWe studied the long-term effect of ileal transposition (IT) metabolic surgery on the hepatokines: retinol-binding protein-4 (RBP4), α-2-HS-glycoprotein (aHSG/fetuin-A), and fibroblast growth factor 21 (FGF21), C-reactive protein (CRP) plasma levels, glucose metabolism, body weight, liver histology, as well as total lipids concentration in muscle, liver, and fat tissue of obese Zucker (Crl:ZUC(ORL)-Leprfa) rats. 14 adult males were randomly submitted either to IT or SHAM (control) surgery. Pre-operative hepatokines plasma levels were not significantly different in rats submitted to IT or SHAM protocol. Three months after the procedures the plasma levels of RBP4, aHSG, FGF21, and CRP were significantly lower in IT-operated animals when compared to SHAM-operated group. Three and 12 weeks after the IT and SHAM surgery, the AUCOGTT were significantly lower than AUCOGTT before the surgery. HOMA-IR was lower in rats after IT surgery in comparison to the SHAM-operated rats. Muscle and liver total lipids concentration was reduced after the IT procedure when compared to pre-IT conditions. IT had a significant reductive impact on the body weight in comparison to SHAM surgery in the 4th, 6th, 8th, and 10th week after the surgery. We conclude that IT reduces hepatokines’ plasma concentrations, muscle and liver total lipids concentration but not the inflammatory processes in the liver of Zucker (Crl:ZUC(ORL)-Leprfa) rats.

scholarly journals Neonatal nutritional programming impairs adiponectin effects on energy homeostasis in adult life of male rats

2018 ◽  
Vol 315 (1) ◽  
pp. E29-E37 ◽  
Author(s):  
Mariana Peduti Halah ◽  
Paula Beatriz Marangon ◽  
Jose Antunes-Rodrigues ◽  
Lucila L. K. Elias
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Food Intake ◽  
White Adipose Tissue ◽  
Energy Homeostasis ◽  
Body Weight Gain ◽  
Adult Life ◽  
Male Rats ◽  
Nutritional Programming

Neonatal nutritional changes induce long-lasting effects on energy homeostasis. Adiponectin influences food intake and body weight. The aim of this study was to investigate the effects of neonatal nutritional programming on the central stimulation of adiponectin. Male Wistar rats were divided on postnatal (PN) day 3 in litters of 3 (small litter, SL), 10 (normal litter, NL), or 16 pups/dam (large litter, LL). We assessed body weight gain for 60 days, adiponectin concentration, and white adipose tissue weight. We examined the response of SL, NL, and LL rats on body weight gain, food intake, oxygen consumption (V̇o2), respiratory exchange ratio (RER), calorimetry, locomotor activity, phosphorylated-AMP-activated protein kinase (AMPK) expression in the hypothalamus, and uncoupling protein (UCP)-1 in the brown adipose tissue after central stimulus with adiponectin. After weaning, SL rats maintained higher body weight gain despite similar food intake compared with NL rats. LL rats showed lower body weight at weaning, with a catch up afterward and higher food intake. Both LL and SL groups had decreased plasma concentrations of adiponectin at PN60. SL rats had increased white adipose tissue. Central injection of adiponectin decreased body weight and food intake and increased V̇o2, RER, calorimetry, p-AMPK and UCP- 1 expression in NL rats, but it had no effect on SL and LL rats, compared with the respective vehicle groups. In conclusion, neonatal under- and overfeeding induced an increase in body weight gain in juvenile and early adult life. Unresponsiveness to central effects of adiponectin contributes to the imbalance of the energy homeostasis in adult life induced by neonatal nutritional programming.

A comparison of the effects of infection with Eimeria maxima and dietary restriction on weight gain, plasma metabolites and liver glycogen in the immature fowl, Gallus domesticus

Parasitology ◽  
1982 ◽  
Vol 84 (2) ◽  
pp. 205-213 ◽  
Author(s):  
H. D. Chapman ◽  
D. L. Fernandes ◽  
T. F. Davison
Keyword(s):  
Growth Rate ◽  
Body Weight ◽  
Uric Acid ◽  
Weight Gain ◽  
Food Intake ◽  
Acute Phase ◽  
Plasma Glucose ◽  
Liver Glycogen ◽  
Plasma Metabolites ◽  
Eimeria Maxima

SUMMARYThe effects of Eimeria maxima or restricted pair-feeding on weight gain, plasma concentrations of protein, glucose, free fatty acids (FFA) and uric acid and liver glycogen were compared in immature fowl. Food intake/kg body weight and weight gain decreased during the acute phase of infection (days 5–7) while weight loss was prolonged for an extra day compared with pair-fed birds. During recovery, food intake/kg body weight of infected birds was greater than that of non-infected controls but there was no evidence for an increase in growth rate compared with controls when body weight was considered. Growth rate of pair-fed birds was greater than that of infected birds during recovery, indicating their better use of ingested food. Liver glycogen and plasma protein concentration were decreased during the acute phase of infection but the concentrations of plasma glucose, free fatty acid (FFA) and uric acid were not affected. In pair-fed birds liver glycogen was depleted, concentrations of plasma glucose and uric acid decreased and FFA increased, and these changes persisted for the remainder of the experiment. The findings are similar to those in birds whose food has been withheld and were probably due to the pattern of food intake imposed by the experimental protocol. It is concluded that the metabolic differences between infected and pair-fed birds are of doubtful significance.

LPS inhibits fasted plasma ghrelin levels in rats: role of IL-1 and PGs and functional implications

2006 ◽  
Vol 291 (4) ◽  
pp. G611-G620 ◽  
Author(s):  
Lixin Wang ◽  
Nicole R. Basa ◽  
Almaas Shaikh ◽  
Andrew Luckey ◽  
David Heber ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Gastric Emptying ◽  
Food Intake ◽  
Intravenous Injection ◽  
Plasma Levels ◽  
Inhibitory Action ◽  
Functional Implications ◽  
Urocortin 1 ◽  
Fasted Rats

LPS injected intraperitoneally decreases fasted plasma levels of ghrelin at 3 h postinjection in rats. We characterized the inhibitory action of LPS on plasma ghrelin and whether exogenous ghrelin restores LPS-induced suppression of food intake and gastric emptying in fasted rats. Plasma ghrelin and insulin and blood glucose were measured after intraperitoneal injection of LPS, intravenous injection of IL-1β and urocortin 1, and in response to LPS under conditions of blockade of IL-1 or CRF receptors by subcutaneous injection of IL-1 receptor antagonist (IL-1Ra) or astressin B, respectively, and prostaglandin (PG) synthesis by intraperitoneal indomethacin. Food intake and gastric emptying were measured after intravenous injection of ghrelin at 5 h postintraperitoneal LPS injection. LPS inhibited the elevated fasted plasma ghrelin levels by 47.6 ± 4.9%, 58.9 ± 3.3%, 74.4 ± 2.7%, and 48.9 ± 8.7% at 2, 3, 5, and 7 h postinjection, respectively, and values returned to preinjection levels at 24 h. Insulin levels were negatively correlated to those of ghrelin, whereas there was no significant correlation between glucose and ghrelin. IL-1Ra and indomethacin prevented the first 3-h decline in ghrelin levels induced by LPS, whereas astressin B did not. IL-1β inhibited plasma ghrelin levels, whereas urocortin 1 had no influence. Ghrelin injected intravenously prevented an LPS-induced 87% reduction of gastric emptying and 61% reduction of food intake. These data showed that IL-1 and PG pathways are part of the early mechanisms by which LPS suppresses fasted plasma ghrelin and that exogenous ghrelin can normalize LPS-induced-altered digestive functions.

scholarly journals The Gut Microbiome Derived From Anorexia Nervosa Patients Impairs Weight Gain and Behavioral Performance in Female Mice

Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2441-2452 ◽  
Author(s):  
Tomokazu Hata ◽  
Noriyuki Miyata ◽  
Shu Takakura ◽  
Kazufumi Yoshihara ◽  
Yasunari Asano ◽  
...  
Keyword(s):  
Body Weight ◽  
Anorexia Nervosa ◽  
Weight Gain ◽  
Food Intake ◽  
Brain Stem ◽  
Body Weight Gain ◽  
Field Tests ◽  
Compulsive Behavior ◽  
The Brain ◽  
Poor Weight Gain

Abstract Anorexia nervosa (AN) results in gut dysbiosis, but whether the dysbiosis contributes to AN-specific pathologies such as poor weight gain and neuropsychiatric abnormalities remains unclear. To address this, germ-free mice were reconstituted with the microbiota of four patients with restricting-type AN (gAN mice) and four healthy control individuals (gHC mice). The effects of gut microbes on weight gain and behavioral characteristics were examined. Fecal microbial profiles in recipient gnotobiotic mice were clustered with those of the human donors. Compared with gHC mice, gAN mice showed a decrease in body weight gain, concomitant with reduced food intake. Food efficiency ratio (body weight gain/food intake) was also significantly lower in gAN mice than in gHC mice, suggesting that decreased appetite as well as the capacity to convert ingested food to unit of body substance may contribute to poor weight gain. Both anxiety-related behavior measured by open-field tests and compulsive behavior measured by a marble-burying test were increased only in gAN mice but not in gHC mice. Serotonin levels in the brain stem of gAN mice were lower than those in the brain stem of gHC mice. Moreover, the genus Bacteroides showed the highest correlation with the number of buried marbles among all genera identified. Administration of Bacteroides vulgatus reversed compulsive behavior but failed to exert any substantial effect on body weight. Collectively, these results indicate that AN-specific dysbiosis may contribute to both poor weight gain and mental disorders in patients with AN.

scholarly journals Effects of sleeve gastrectomy and ileal transposition, alone and in combination, on food intake, body weight, gut hormones, and glucose metabolism in rats

2013 ◽  
Vol 305 (4) ◽  
pp. E507-E518 ◽  
Author(s):  
S. Nausheen ◽  
I. H. Shah ◽  
A. Pezeshki ◽  
D. L. Sigalet ◽  
P. K. Chelikani
Keyword(s):  
Body Weight ◽  
Sleeve Gastrectomy ◽  
Weight Gain ◽  
Food Intake ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Gut Hormones ◽  
Ileal Transposition ◽  
Gastric Restriction ◽  
Peripheral Tissues

Bariatric surgeries are hypothesized to produce weight loss and improve diabetes control by multiple mechanisms including gastric restriction and lower gut stimulation; the relative importance of these mechanisms remains poorly understood. We compared the effects of a typical foregut procedure, sleeve gastrectomy, (SG) with a primarily hindgut surgery, ileal transposition (IT), alone and together (SGIT), or sham manipulations, on food intake, body weight, gut hormones, glucose tolerance, and key markers of glucose homeostasis in peripheral tissues of adult male Sprague-Dawley rats (450–550 g, n = 7–9/group). SG, IT, and SGIT surgeries produced transient reduction in food intake and weight gain; the effects of SG and IT on intake and body weight were nonadditive. SG, IT, and SGIT surgeries resulted in increased tissue expression and plasma concentrations of the lower gut hormones glucagon-like peptide-1 and peptide YY and decreased plasma glucose-dependent insulinotropic peptide, insulin, and leptin concentrations. Despite transient effects on intake and weight gain, the SG, IT, and SGIT surgeries produced a significant improvement in glucose tolerance. In support of glycemic improvements, the protein abundance of key markers of glucose metabolism (e.g., GLUT4, PKA, IRS-1) in muscle and adipose tissue were increased, whereas the expression of key gluconeogenic enzyme in liver (G-6-Pase) were decreased following the surgeries. Therefore, our data suggest that enhanced lower gut stimulation following SG, IT, and SGIT surgeries leads to transient reduction in food intake and weight gain together with enhanced secretion of lower gut hormones and improved glucose clearance by peripheral tissues.

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