scholarly journals Dipeptidyl peptidase‐4 inhibitor lowers PPARγ agonist‐induced body weight gain by affecting food intake, fat mass and beige/brown fat but not fluid retention (1160.9)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Yiling Fu ◽  
Takahiro Masuda ◽  
Akiko Eguchi ◽  
Jan Czogalla ◽  
Michael Rose ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Fat Mass ◽  
Body Weight Gain ◽  
Dipeptidyl Peptidase ◽  
Fluid Retention ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
Pparγ Agonist

scholarly journals Dipeptidyl peptidase IV inhibitor lowers PPARγ agonist-induced body weight gain by affecting food intake, fat mass, and beige/brown fat but not fluid retention

2014 ◽  
Vol 306 (4) ◽  
pp. E388-E398 ◽  
Author(s):  
Takahiro Masuda ◽  
Yiling Fu ◽  
Akiko Eguchi ◽  
Jan Czogalla ◽  
Michael A. Rose ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Fat Mass ◽  
Fluid Retention ◽  
Dipeptidyl Peptidase Iv ◽  
Brown Fat ◽  
Antidiabetic Drugs ◽  
Dpp Iv ◽  
Pparγ Agonist

Peroxisome proliferator-activated receptor-γ (PPARγ) agonists like pioglitazone (PGZ) are effective antidiabetic drugs, but they induce fluid retention and body weight (BW) gain. Dipeptidyl peptidase IV (DPP IV) inhibitors are antidiabetic drugs that enhance renal Na+ and fluid excretion. Therefore, we examined whether the DPP IV inhibitor alogliptin (ALG) ameliorates PGZ-induced BW gain. Male Sv129 mice were treated with vehicle (repelleted diet), PGZ (220 mg/kg diet), ALG (300 mg/kg diet), or a combination of PGZ and ALG (PGZ + ALG) for 14 days. PGZ + ALG prevented the increase in BW observed with PGZ but did not attenuate the increase in body fluid content determined by bioimpedance spectroscopy (BIS). BIS revealed that ALG alone had no effect on fat mass (FM) but enhanced the FM-lowering effect of PGZ; MRI analysis confirmed the latter and showed reductions in visceral and inguinal subcutaneous (sc) white adipose tissue (WAT). ALG but not PGZ decreased food intake and plasma free fatty acid concentrations. Conversely, PGZ but not ALG increased mRNA expression of thermogenesis mediator uncoupling protein 1 in epididymal WAT. Adding ALG to PGZ treatment increased the abundance of multilocular cell islets in sc WAT, and PGZ + ALG increased the expression of brown-fat-like “beige” cell marker TMEM26 in sc WAT and interscapular brown adipose tissue and increased rectal temperature vs. vehicle. In summary, DPP IV inhibition did not attenuate PPARγ agonist-induced fluid retention but prevented BW gain by reducing FM. This involved ALG inhibition of food intake and was associated with food intake-independent synergistic effects of PPARγ agonism and DPP-IV inhibition on beige/brown fat cells and thermogenesis.

scholarly journals Commensal Hafnia alvei strain reduces food intake and fat mass in obese mice—a new potential probiotic for appetite and body weight management

2020 ◽  
Vol 44 (5) ◽  
pp. 1041-1051 ◽  
Author(s):  
Romain Legrand ◽  
Nicolas Lucas ◽  
Manon Dominique ◽  
Saida Azhar ◽  
Camille Deroissart ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Weight Management ◽  
Fat Mass ◽  
Body Weight Gain ◽  
Overweight And Obesity ◽  
Obese Mice ◽  
Hafnia Alvei ◽  
Reduced Body

Abstract Background/objectives Based on the recent identification of E.coli heat shock protein ClpB as a mimetic of the anorexigenic α-melanocyte stimulating hormone (α-MSH), the objective of this study was to preclinically validate Hafnia alvei, a ClpB-producing commensal bacterium as a potential probiotic for appetite and body weight management in overweight and obesity. Methods The involvement of enterobacterial ClpB in the putative anti-obesity effects was studied using ClpB-deficient E.coli. A food-grade H. alvei HA4597 strain synthetizing the ClpB protein with an α-MSH-like motif was selected as a candidate probiotic to be tested in ob/ob and high-fat diet (HFD)-fed obese and overweight mice. The relevance of the enterobacterial ClpB gene to human obesity was studied by in silico analysis of fecal metagenomes of 569 healthy individuals from the “MetaHIT” database. Results Chronic per os administration of native but not ClpB-deficient E.coli strain reduced body weight gain (p < 0.05) and daily meal frequency (p < 0.001) in ob/ob mice. Oral gavage of H.alvei for 18 and 46 days in ob/ob and HFD-fed obese mice, respectively, was well tolerated, reduced body weight gain and fat mass in both obesity models (p < 0.05) and decreased food intake in hyperphagic ob/ob mice (p < 0.001). Elevated fat tissue levels of phosphorylated hormone-sensitive lipase were detected in H.alvei -treated ob/ob mice (p < 0.01). Enterobacterial ClpB gene richness was lower in obese vs. non-obese humans (p < 0.0001) and correlated negatively with BMI in genera of Enterobacter, Klebsiella and Hafnia. Conclusions H.alvei HA4597 strain reduces food intake, body weight and fat mass gain in hyperphagic and obese mice. These data combined with low enterobacterial ClpB gene abundance in the microbiota of obese humans provide the rationale for using H.alvei as a probiotic for appetite and body weight management in overweight and obesity.

scholarly journals Tetrahydrocannabinolic Acid a (THCA-A) Reduces Adiposity and Prevents Metabolic Disease Caused by Diet-Induced Obesity

2019 ◽  
Author(s):  
Belén Palomares ◽  
Francisco Ruiz-Pino ◽  
Martin Garrido-Rodriguez ◽  
M. Eugenia Prados ◽  
Miguel A. Sánchez-Garrido ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Fat Mass ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Liver Steatosis ◽  
High Fat ◽  
Present Evidence ◽  
Pparγ Agonist ◽  
Psychotropic Effects

ABSTRACTCannabis has remarkable therapeutic potential, but its clinical use is limited by the psychotropic activity of Δ9-tetrahydrocannabinol (Δ9-THC). Surprisingly, the biological profile of the non-narcotic native precursor of Δ9-THC (Δ9-THC acid A, Δ9-THCA-A) is still largely unexplored. We present evidence that Δ9-THCA-A is a partial and selective PPARγ modulator, endowed with lower adipogenic activity than the full PPARγ agonist rosiglitazone (RGZ) and with an enhanced osteoblastogenic activity in human mesenchymal stem cells. Docking andin vitrofunctional assays indicated that Δ9-THCA-A binds to and activates PPARγ by acting at both the canonical and the alternative sites of the ligand-binding domain. Transcriptomic signatures at inguinal white adipose tissue (iWAT) from mice treated with Δ9-THCA-A confirmed its mode of action on PPARγ. Administration of Δ9-THCA-A in a mouse model of high fat diet (HFD)-induced obesity significantly reduced fat mass and body weight gain, markedly ameliorating glucose intolerance and insulin resistance, and largely preventing liver steatosis, adipogenesis and macrophage infiltration in fat tissues. Additionally, immunohistochemistry, transcriptomic, and plasma biomarker analyses showed that treatment with Δ9-THCA-A caused browning of iWAT and displayed potent anti-inflammatory actions in HFD mice. Altogether, our data validate the potential of Δ9-THCA-A as a low adipogenic PPARγ agonist, capable of substantially improving the symptoms of obesity-associated metabolic syndrome and inflammation. These findings suggest that Δ9-THCA-A, and perhaps non-decarboxylatedCannabis sativaextracts, are worth considering for addition to our inventory of cannabis medicines.SIGNIFICANCE STATEMENTThe medicinal use of Cannabis is gaining momentum, despite the adverse psychotropic effects of Δ9-THC, the decarboxylation product of its naturally occurring and non-psychotropic precursor Δ9-THCA-A. We present evidence that Δ9-THCA-A is a partial ligand agonist of PPARγ with lower adipogenic activity compared to the full PPARγ agonist rosiglitazone (RGZ). Moreover, chronic administration of Δ9-THCA-A in a mouse model of high fat diet (HFD)-induced obesity significantly reduced body weight gain and fat mass, improved glucose intolerance and insulin resistance, and prevented liver steatosis and macrophage infiltration in fat tissues, additionally inducing white adipose tissue browning. Collectively, these observations qualify Δ9-THCA-A, a compound devoid of psychotropic effects, as an efficacious pharmacological agent to manage metabolic syndrome and obesity-associated inflammation.Highlights- Δ9-THCA-A is a partial PPARγ ligand agonist with low adipogenic activity- Δ9-THCA-A enhances osteoblastogenesis in bone marrow derived mesenchymal stem cells.- Δ9-THCA-A reduces body weight gain, fat mass, and liver steatosis in HFD-fed mice- Δ9-THCA-A improves glucose tolerance, insulin sensitivity, and insulin profilesin vivo- Δ9-THCA-A induces browning of iWAT and has a potent anti-inflammatory activity

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.

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.

Bimatoprost promotes satiety and attenuates body weight in rats fed standard or obesity-promoting diets.

2020 ◽  
Author(s):  
Clayton Spada ◽  
Chau Vu ◽  
Iona Raymond ◽  
Warren Tong ◽  
Chia-Lin Chuang ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Gastric Emptying ◽  
Food Intake ◽  
Visceral Fat ◽  
Body Weight Gain ◽  
Metabolic Effects ◽  
Sprague Dawley ◽  
Hormone Levels ◽  
Gut Hormone

Abstract Background Bimatoprost negatively regulates adipogenesis in vitro and likely participates in a negative feedback loop on anandamide-induced adipogenesis. Here, we investigate the broader metabolic effects of bimatoprost action in vivo in rats under both normal state and obesity-inducing conditions. Methods Male Sprague Dawley rats were a fed standard chow (SC) diet in conjunction with dermally applied bimatoprost treatment for a period of 9–10 weeks. Body weight gain, energy expenditure, food intake, and hormones associated with satiety were measured. Gastric emptying was also separately evaluated. In obesity-promoting diet studies, rats were fed a cafeteria diet (CAF) and gross weight, fat accumulation in SQ, visceral fat and liver was evaluated together with standard serum chemistry. Results Chronic bimatoprost administration attenuated weight gain in rats fed either standard or obesity-promoting diets over a 9–10 weeks. Bimatoprost increased satiety as measured by decreased food intake, gastric emptying and circulating gut hormone levels. Additionally, SQ and visceral fat mass was distinctly affected by treatment. Bimatoprost increased satiety as measured by decreased food intake, gastric emptying and circulating gut hormone levels. Conclusions These findings suggest that bimatoprost (and possibly prostamide F2α) regulates energy homeostasis through actions on dietary intake. These actions likely counteract the metabolic actions of anandamide through the endocannabinoid system potentially revealing a new pathway that could be exploited for therapeutic development.

scholarly journals Oxytocin Administration Alleviates Acute but Not Chronic Leptin Resistance of Diet-Induced Obese Mice

2018 ◽  
Vol 20 (1) ◽  
pp. 88 ◽  
Author(s):  
Mehdi Labyb ◽  
Chloé Chrétien ◽  
Aurélie Caillon ◽  
Françoise Rohner-Jeanrenaud ◽  
Jordi Altirriba
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Leptin Resistance ◽  
Obese Mice ◽  
Short Term ◽  
Continuous Administration ◽  
Pre Treatment ◽  
Treatment Of Obesity

Whereas leptin administration only has a negligible effect on the treatment of obesity, it has been demonstrated that its action can be improved by co-administration of leptin and one of its sensitizers. Considering that oxytocin treatment decreases body weight in obese animals and humans, we investigated the effects of oxytocin and leptin cotreatment. First, lean and diet-induced obese (DIO) mice were treated with oxytocin for 2 weeks and we measured the acute leptin response. Second, DIO mice were treated for 2 weeks with saline, oxytocin (50 μg/day), leptin (20 or 40 µg/day) or oxytocin plus leptin. Oxytocin pre-treatment restored a normal acute leptin response, decreasing food intake and body weight gain. Chronic continuous administration of oxytocin or leptin at 40 µg/day decreased body weight in the presence (leptin) or in the absence (oxytocin) of cumulative differences in food intake. Saline or leptin treatment at 20 µg/day had no impact on body weight. Oxytocin and leptin cotreatments had no additional effects compared with single treatments. These results point to the fact that chronic oxytocin treatment improves the acute, but not the chronic leptin response, suggesting that this treatment could be used to improve the short-term satiety effect of leptin.

scholarly journals Effects of Consuming Sugar-Sweetened Beverages for 2 Weeks on 24-h Circulating Leptin Profiles, Ad Libitum Food Intake and Body Weight in Young Adults

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3893 ◽  
Author(s):  
Desiree M. Sigala ◽  
Adrianne M. Widaman ◽  
Bettina Hieronimus ◽  
Marinelle V. Nunez ◽  
Vivien Lee ◽  
...  
Keyword(s):  
Young Adults ◽  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Energy Intake ◽  
Body Weight Gain ◽  
Energy Requirement ◽  
Area Under The Curve ◽  
Sugar Sweetened Beverage ◽  
Ad Libitum

Sugar-sweetened beverage (sugar-SB) consumption is associated with body weight gain. We investigated whether the changes of (Δ) circulating leptin contribute to weight gain and ad libitum food intake in young adults consuming sugar-SB for two weeks. In a parallel, double-blinded, intervention study, participants (n = 131; BMI 18–35 kg/m2; 18–40 years) consumed three beverages/day containing aspartame or 25% energy requirement as glucose, fructose, high fructose corn syrup (HFCS) or sucrose (n = 23–28/group). Body weight, ad libitum food intake and 24-h leptin area under the curve (AUC) were assessed at Week 0 and at the end of Week 2. The Δbody weight was not different among groups (p = 0.092), but the increases in subjects consuming HFCS- (p = 0.0008) and glucose-SB (p = 0.018) were significant compared with Week 0. Subjects consuming sucrose- (+14%, p < 0.0015), fructose- (+9%, p = 0.015) and HFCS-SB (+8%, p = 0.017) increased energy intake during the ad libitum food intake trial compared with subjects consuming aspartame-SB (−4%, p = 0.0037, effect of SB). Fructose-SB decreased (−14 ng/mL × 24 h, p = 0.0006) and sucrose-SB increased (+25 ng/mL × 24 h, p = 0.025 vs. Week 0; p = 0.0008 vs. fructose-SB) 24-h leptin AUC. The Δad libitum food intake and Δbody weight were not influenced by circulating leptin in young adults consuming sugar-SB for 2 weeks. Studies are needed to determine the mechanisms mediating increased energy intake in subjects consuming sugar-SB.

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