Ptp1b deletion in pro-opiomelanocortin neurons increases energy expenditure and impairs endothelial function via TNF-α dependent mechanisms

2016 ◽  
Vol 130 (11) ◽  
pp. 881-893 ◽  
Author(s):  
Thiago Bruder-Nascimento ◽  
Simone Kennard ◽  
Galina Antonova ◽  
James D. Mintz ◽  
Kendra K. Bence ◽  
...  

The present study suggests that although increasing energy expenditure might be an efficient therapy to reduce body weight and prevent diabetes, it might have deleterious effects on the cardiovascular system and notably promotes the development of vascular dysfunction.

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Lissette Duarte ◽  
Luis Amanda Ramirez ◽  
Javier Quezada ◽  
Carlos Poblete ◽  
Francisca Concha ◽  
...  

Abstract Objectives To evaluate the effect of a polyphenol-rich berberis microphylla (Calafate, a Chilean native berry) extract in obese mice. Methods 40 8-week old C57BL6 mice were divided (n = 10 each) in 4 treatments for 4 months: Control diet (C; 11% fat), Control diet/Calafate (CC), High fat diet (HF; 58% fat), and High fat diet/Calafate (HFC). Animals received food and water ad libitum. CC and HFC were treated with a daily dose of 50 mg total polyphenols/kg weight of Calafate extract. IPGTT and indirect calorimetry were performed at month 2 and 3 respectively. At month 4, animals were euthanized and final body weight were recorded, and samples of interscapular brown (BAT), epididymal white (eWAT) and inguinal white (iWAT) adipose tissues were obtained. Gene expression of inflammatory markers (MCP-1, TNF-α, Leptina, ADIPOQ and F4/80) on eWAT and thermogenic markers (UCP-1, PGC1α, SIRT1, PRDM16, PPARα/γ, DIO2) on BAT and iWAT were analyzed. 2x2 ANOVA statistical analysis was applied. Results HF presented higher body weight than HFC mice (p < 0.001), from day 40 of treatment. Also, BAT weight was increased (p < 0.05). Basal glycemia was higher in HF than C (p < 0.05), but not than HFC. Energy expenditure was higher in HFC (p < 0.05). Differential expression of MCP-1, leptin and F4/80 on eWAT was detected. In BAT, UCP-1, PGC1α, PPARα and SIRT1 expression were higher in HFC than HF (p < 0.05). In iWAT, expression of PGC1α, PPARα, PRDM16, SIRT1, y DIO2 were also increased (p < 0.05). Conclusions a polyphenol-rich Calafate extract decrease body weight increase, augment BAT mass, modulate inflammation, and promote energy expenditure, which was related to higher expression of thermogenic genes in obese mice. Funding Sources FONDECYT 1171550 (CONICYT, CHILE).


Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 442
Author(s):  
Debora Muratori Holanda ◽  
Young Ihn Kim ◽  
Wanpuech Parnsen ◽  
Sung Woo Kim

Phytobiotics with a mycotoxin adsorbent were used to mitigate negative effects of multiple mycotoxins in diets fed to pigs. In experiment 1, 120 pigs (11.6 kg body weight; BW) were assigned to five treatments (three pigs/pen) and fed for 28 days. Treatments were CON (control), MTD (CON + 2.5 mg/kg of deoxynivalenol), DP (MTD + phytobiotics at 0.1%), and DPA1 and DPA2 (MTD + phytobiotics and adsorbent at 0.1% and 0.2%, respectively). In experiment 2, 96 pigs (28.5 kg BW) were assigned to four treatments (three pigs/pen) and fed for 26 days. Treatments were CON, MTAF (CON + 0.19 mg/kg of aflatoxin and 8 mg/kg of fumonisins), AFP (MTAF + phytobiotics at 0.1%), and AFPA (MTAF + phytobiotics and adsorbent at 0.1%). Growth performance was measured weekly, and blood was sampled at the end of study to measure hepatic function and inflammatory status (TNF-α). Data were analyzed using the MIXED procedure. In experiment 1, pigs fed MTD, DP, DPA1, and DPA2 had smaller (p < 0.05) BW than CON. Pigs fed DPA2 had greater (p < 0.05) BW than MTD. Pigs fed DP and DPA2 tended to have lower (p < 0.1) serum total protein than CON. Pigs fed MTD and DPA2 tended to have higher (p < 0.1) alanine aminotransferase than CON. Similarly, pigs fed MTD, DP, and DPA2 tended to have higher (p < 0.1) urea nitrogen/creatinine than CON. In experiment 2, pigs fed MTAF, AFP, and AFPA had smaller (p < 0.05) BW than CON. Pigs fed MTAF, AFP, and AFPA had smaller (p < 0.05) ADFI than CON. Pigs fed AFPA had higher (p < 0.05) aspartate aminotransferase than CON and MTAF. Pigs fed AFP and AFPA had higher (p < 0.05) alanine aminotransferase than CON. Pigs fed MTAF, AFP, and AFPA had lower (p < 0.05) urea nitrogen/creatinine than CON. Pigs fed AFPA had higher (p < 0.05) TNF-α than CON and MTAF. In conclusion, feeding an additional 2.5 mg/kg of deoxynivalenol or 0.19 mg/kg of aflatoxin with 8 mg/kg of fumonisins reduced the growth of pigs. Deoxynivalenol compromised the hepatic function of pigs. Phytobiotics with adsorbent could partly overcome the detrimental effects of mycotoxins.


2021 ◽  
pp. 1098612X2110137
Author(s):  
James R Templeman ◽  
Kylie Hogan ◽  
Alexandra Blanchard ◽  
Christopher PF Marinangeli ◽  
Alexandra Camara ◽  
...  

Objectives The objective of this study was to verify the safety of policosanol supplementation for domestic cats. The effects of raw and encapsulated policosanol were compared with positive (L-carnitine) and negative (no supplementation) controls on outcomes of complete blood count, serum biochemistry, energy expenditure, respiratory quotient and physical activity in healthy young adult cats. Methods The study was a replicated 4 × 4 complete Latin square design. Eight cats (four castrated males, four spayed females; mean age 3.0 ± 1.0 years; mean weight 4.36 ± 1.08 kg; mean body condition score 5.4 ± 1.4) were blocked by sex and body weight then randomized to treatment groups: raw policosanol (10 mg/kg body weight), encapsulated policosanol (50 mg/kg body weight), L-carnitine (200 mg/kg body weight) or no supplementation. Treatments were supplemented to a basal diet for 28 days with a 1-week washout between periods. Food was distributed equally between two offerings to ensure complete supplement consumption (first offering) and measure consumption time (second offering). Blood collection (lipid profile, complete blood count, serum biochemistry) and indirect calorimetry (energy expenditure, respiratory quotient) were conducted at days 0, 14 and 28 of each period. Activity monitors were worn 7 days prior to indirect calorimetry and blood collection. Data were analyzed using a repeated measures mixed model (SAS, v.9.4). Results Food intake and body weight were similar among treatments. There was no effect of treatment on lipid profile, serum biochemistry, activity, energy expenditure or respiratory quotient ( P >0.05); however, time to consume a second meal was greatest in cats fed raw policosanol ( P <0.05). Conclusions and relevance These data suggest that policosanol is safe for feline consumption. Further studies with cats demonstrating cardiometabolic risk factors are warranted to confirm whether policosanol therapy is an efficacious treatment for hyperlipidemia and obesity.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1127
Author(s):  
Juan Sendon-Lago ◽  
Lorena Garcia-del Rio ◽  
Noemi Eiro ◽  
Patricia Diaz-Rodriguez ◽  
Leandro Avila ◽  
...  

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasingly prevalent and current therapies are not completely effective. Mesenchymal stem cells are emerging as a promising therapeutic option. Here, the effect of local hydrogel application loaded with conditioned medium (CM) from human uterine cervical stem cells (hUCESC-CM) in an experimental acute colitis mice model has been evaluated. Colitis induction was carried out in C57BL/6 mice by dissolving dextran sulfate sodium (DSS) in drinking water for nine days. Ulcers were treated by rectal administration of either mesalazine (as positive control) or a mucoadhesive and thermosensitive hydrogel loaded with hUCESC-CM (H-hUCESC-CM). Body weight changes, colon length, and histopathological analysis were evaluated. In addition, pro-inflammatory TNF-α, IL-6, and IFN-γ mRNA levels were measured by qPCR. Treatment with H-hUCESC-CM inhibited body weight loss and colon shortening and induced a significant decrease in colon mucosa degeneration, as well as TNF-α, IFN-γ, and IL-6 mRNA levels. Results indicate that H-hUCESC-CM effectively alleviated DSS-induced colitis in mice, suggesting that H-hUCESC-CM may represent an attractive cell-free therapy for local treatment of IBD.


EFSA Journal ◽  
2019 ◽  
Vol 17 (6) ◽  
Author(s):  
◽  
Dominique Turck ◽  
Jacqueline Castenmiller ◽  
Stefaan De Henauw ◽  
Karen Ildico Hirsch‐Ernst ◽  
...  

1999 ◽  
Vol 276 (5) ◽  
pp. R1425-R1433 ◽  
Author(s):  
Gertjan van Dijk ◽  
Randy J. Seeley ◽  
Todd E. Thiele ◽  
Mark I. Friedman ◽  
Hong Ji ◽  
...  

To investigate whether brain leptin involves neuropeptidergic pathways influencing ingestion, metabolism, and gastrointestinal functioning, leptin (3.5 μg) was infused daily into the third cerebral ventricular of rats for 3 days. To distinguish between direct leptin effects and those secondary to leptin-induced anorexia, we studied vehicle-infused rats with food available ad libitum and those that were pair-fed to leptin-treated animals. Although body weight was comparably reduced (−8%) and plasma glycerol was comparably increased (142 and 17%, respectively) in leptin-treated and pair-fed animals relative to controls, increases in plasma fatty acids and ketones were only detected (132 and 234%, respectively) in pair-fed rats. Resting energy expenditure (−15%) and gastrointestinal fill (−50%) were reduced by pair-feeding relative to the ad libitum group, but they were not reduced by leptin treatment. Relative to controls, leptin increased hypothalamic mRNA for corticotropin-releasing hormone (CRH; 61%) and for proopiomelanocortin (POMC; 31%) but did not reduce mRNA for neuropeptide Y. These results suggest that CNS leptin prevents metabolic/gastrointestinal responses to caloric restriction by activating hypothalamic CRH- and POMC-containing pathways and raise the possibility that these peripheral responses to CNS leptin administration contribute to leptin’s anorexigenic action.


1991 ◽  
Vol 81 (5) ◽  
pp. 635-644 ◽  
Author(s):  
Alan A. Connacher ◽  
William M. Bennet ◽  
Roland T. Jung ◽  
Dennis M. Bier ◽  
Christopher C. T. Smith ◽  
...  

1. Energy expenditure, plasma glucose and palmitate kinetics and leg glycerol release were determined simultaneously both before and during adrenaline infusion in lean and obese human subjects. Seven lean subjects (mean 96.5% of ideal body weight) were studied in the post-absorptive state and also during mixed nutrient liquid feeding, eight obese subjects (mean 165% of ideal body weight) were studied in the post-absorptive state and six obese subjects (mean 174% of ideal body weight) were studied during feeding. 2. Resting energy expenditure was higher in the obese subjects, but the thermic response to adrenaline, both in absolute and percentage terms, was similar in lean and obese subjects. Plasma adrenaline concentrations attained (3 nmol/l) were comparable in all groups and the infusion had no differential effects on the plasma insulin concentration. Before adrenaline infusion the plasma glucose flux was higher in the obese than in the lean subjects in the fed state only (45.8 ± 3.8 versus 36.6 ± 1.0 mmol/h, P <0.05); it increased to the same extent in both groups with the adrenaline infusion. 3. Before the adrenaline infusion plasma palmitate flux was higher in the obese than in the lean subjects (by 51%, P <0.01, in the post-absorptive state and by 78%, P <0.05, in the fed state). However, there was no significant change during adrenaline infusion in the obese subjects (from 13.5 ± 1.00 to 15.0 ± 1.84 mmol/h, not significant, in the post-absorptive state and from 14.4 ± 2.13 to 15.7 ± 1.74 mmol/h, not significant, in the fed state), whereas there were increases in the lean subjects (from 8.93 ± 1.10 to 11.2 ± 1.19 mmol/h, P <0.05, in the post-absorptive state, and from 8.06 ± 1.19 to 9.86 ± 0.93 mmol/h, P <0.05, in the fed state). 4. Before adrenaline infusion the palmitate oxidation rate was also higher in the obese than in the lean subjects (1.86 ± 0.14 versus 1.22 ± .09 mmol/h, P <0.01, in the post-absorptive state and 1,73 ± 0.25 versus 1.12 ± 0.12 mmol/h, P <0.05, in the fed state). However, in response to adrenaline the fractional oxidation rate (% of flux) increased less in the obese than in the lean subjects, especially in the post-absorptive state (from 13.8 ± 1.02 to 14.9 ± 1.39%, not significant, versus from 13.7 ± 0.98 to 19.3 ± 1.92%, P <0.05). These effects were independent of feeding. Leg glycerol release increased more in the lean subjects with adrenaline infusion, although increases in the plasma glycerol concentration did not differ between the groups. 5. These results suggest that in obese subjects plasma inter-organ transport of fatty acids and the subsequent fractional oxidation responses favour storage of triacylglycerol. These factors may be important determinants for the development and maintenance of the obese state.


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