scholarly journals Manipulation of dietary amino acids prevents and reverses obesity in mice through multiple mechanisms that modulate energy homeostasis

2020 ◽  
Author(s):  
Ada Admin ◽  
Chiara Ruocco ◽  
Maurizio Ragni ◽  
Fabio Rossi ◽  
Pierluigi Carullo ◽  
...  

Reduced activation of energy metabolism increases adiposity in humans and other mammals. Thus, exploring dietary and molecular mechanisms able to improve energy metabolism is of paramount medical importance, as such mechanisms can be leveraged as a therapy for obesity and related disorders. Here, <a>we show that a designer protein-deprived diet enriched in free essential amino acids can i) promote the brown fat thermogenic program and fatty acid oxidation, ii) stimulate uncoupling protein 1 (UCP1)-independent respiration in subcutaneous white fat, iii) change the gut microbiota composition, and iv) prevent and reverse obesity and dysregulated glucose homeostasis in multiple mouse models, prolonging the healthy lifespan. </a>These effects are independent of unbalanced amino acid ratio, energy consumption, and intestinal calorie absorption. A brown fat-specific activation of the mechanistic target of rapamycin complex 1 seems involved in the diet-induced beneficial effects, as also strengthened by <i>in vitro</i> experiments. Hence, our results suggest that brown and white fat may be targets of specific amino acids to control UCP1-dependent and -independent thermogenesis, thereby contributing to the improvement of metabolic health.

2020 ◽  
Author(s):  
Ada Admin ◽  
Chiara Ruocco ◽  
Maurizio Ragni ◽  
Fabio Rossi ◽  
Pierluigi Carullo ◽  
...  

Reduced activation of energy metabolism increases adiposity in humans and other mammals. Thus, exploring dietary and molecular mechanisms able to improve energy metabolism is of paramount medical importance, as such mechanisms can be leveraged as a therapy for obesity and related disorders. Here, <a>we show that a designer protein-deprived diet enriched in free essential amino acids can i) promote the brown fat thermogenic program and fatty acid oxidation, ii) stimulate uncoupling protein 1 (UCP1)-independent respiration in subcutaneous white fat, iii) change the gut microbiota composition, and iv) prevent and reverse obesity and dysregulated glucose homeostasis in multiple mouse models, prolonging the healthy lifespan. </a>These effects are independent of unbalanced amino acid ratio, energy consumption, and intestinal calorie absorption. A brown fat-specific activation of the mechanistic target of rapamycin complex 1 seems involved in the diet-induced beneficial effects, as also strengthened by <i>in vitro</i> experiments. Hence, our results suggest that brown and white fat may be targets of specific amino acids to control UCP1-dependent and -independent thermogenesis, thereby contributing to the improvement of metabolic health.


1994 ◽  
Vol 266 (6) ◽  
pp. R1765-R1770 ◽  
Author(s):  
C. J. Billington ◽  
J. E. Briggs ◽  
S. Harker ◽  
M. Grace ◽  
A. S. Levine

Intracerebroventricular injection of neuropeptide Y (NPY) has two effects on energy metabolism in addition to increased feeding: decreased brown fat thermogenesis and increased white fat lipoprotein lipase (LPL) enzymatic activity. We hypothesized that the paraventricular nucleus (PVN) of the hypothalamus is the controlling neural site for these responses. We further hypothesized that NPY stimulation at PVN would reduce gene expression for the critical brown fat thermogenic protein, uncoupling protein (UCP), and increase gene expression for the key white fat storage enzyme, LPL. In the first experiment, three groups of rats received injections every 6 h for 24 h (5 injections total) into the PVN:1) NPY (1 micrograms/1 microliters injection) and ad libitum food; 2) NPY (1 micrograms/1 microliters injection) and food restricted to control intake; 3) saline injection (1 microliter) and ad libitum food. Both NPY-treated groups showed significant reductions (P < 0.05) in brown fat UCP mRNA levels and marked stimulation of LPL mRNA levels relative to controls. In the second experiment, four groups of seven rats had NPY injected into the PVN:0 (vehicle control); 0.1 microgram; 0.5 microgram; and 1 microgram. Injections were made every 6 h for 24 h. There was a dose-related reduction in UCP mRNA produced by the NPY treatment. NPY treatment increased LPL mRNA, but a smooth dosing effect was not evident. The observation that NPY in the PVN can coordinate more than one component of energy metabolism is significant when considered with many reports of responsiveness of NPY activity in the arcuate nucleus-PVN neural circuit to perturbations of energy balance such as fasting and feeding, diabetes, and genetic obesity.(ABSTRACT TRUNCATED AT 250 WORDS)


2012 ◽  
Vol 2 (1) ◽  
pp. 1 ◽  
Author(s):  
Hidekatsu Yanai ◽  
Hiroshi Yoshida ◽  
Yuji Hirowatari ◽  
Norio Tada

Characteristics for the serum lipid abnormalities in the obesity/metabolic syndrome are elevated fasting, postprandial triglyceride (TG), and decreased high-density lipoprotein-cholesterol (HDL-C). Diacylglycerol (DAG) oil ingestion has been reported to ameliorate postprandial hyperlipidemia and prevent obesity by increasing energy expenditure, due to the intestinal physiochemical dynamics that differ from triacylglycerol (TAG). Our study demonstrated that DAG suppresses postprandial increase in TG-rich lipoprotein, very low-density lipoprotein (VLDL), and insulin, as compared with TAG in young, healthy individuals. Interestingly, our study also presented that DAG significantly increases plasma serotonin, which is mostly present in the intestine, and mediates thermogenesis, proposing a possible mechanism for a postprandial increase in energy expenditure by DAG. Our other study demonstrated that DAG suppresses postprandial increase in TG, VLDL-C, and remnant-like particle-cholesterol, in comparison with TAG in an apolipoprotein C-II deficient subject, suggesting that DAG suppresses postprandial TG-rich lipoprotein independently of lipoprotein lipase. Further, to understand the molecular mechanisms for DAG-mediated increase in serotonin and energy expenditure, we studied the effects of 1-monoacylglycerol and 2-monoacylglycerol, distinct digestive products of DAG and TAG, respectively, on serotonin release from the Caco-2 cells, the human intestinal cell line. We also studied effects of 1- and 2-monoacylglycerol, and serotonin on the expression of mRNA associated with β-oxidation, fatty acids metabolism, and thermogenesis, in the Caco-2 cells. 1-monoacylglycerol significantly increased serotonin release from the Caco-2 cells, compared with 2-monoacylglycerol by approximately 40%. The expression of mRNA of acyl-CoA oxidase (ACO), fatty acid translocase (FAT), and uncoupling protein-2 (UCP-2), was significantly higher in 1-MOG-treated Caco-2 cells, than 2-MOG-treated cells. The expression of mRNA of ACO, medium-chain acyl-CoA dehydrogenase, FAT, and UCP-2, was significantly elevated in serotonin-treated Caco-2 cells, compared to cells incubated without serotonin. In conclusion, our clinical and in vitro studies suggested a possible therapeutic application of DAG for obesity, and obesity-related metabolic disorders.Key words: Diacylglycerol, intestine, obesity, serotonin, thermogenesis


2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110550
Author(s):  
Xing Wang ◽  
Shuchun Chen ◽  
Dan Lv ◽  
Zelin Li ◽  
Luping Ren ◽  
...  

Objective To investigate the effect of liraglutide on the browning of white fat and the suppression of obesity via regulating microRNA (miR)-27b in vivo and in vitro. Methods Sprague-Dawley rats were fed a high-fat (HF) diet and 3T3-L1 pre-adipocytes were differentiated into mature white adipocytes. Rats and mature adipocytes were then treated with different doses of liraglutide. The mRNA and protein levels of browning-associated proteins, including uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16), CCAAT enhancer binding protein β (CEBPβ), cell death-inducing DFFA-like effector A (CIDEA) and peroxisome proliferator-activated receptor-γ-coactivator 1α (PGC-1α), were detected using quantitative real-time polymerase chain reaction and Western blotting. Results Liraglutide decreased body weight and reduced the levels of blood glucose, triglyceride and low-density lipoprotein cholesterol in HF diet-fed rats. Liraglutide increased the levels of UCP1, PRDM16, CEBPβ, CIDEA and PGC-1α in vivo and vitro. The levels of miR-27b were upregulated in HF diet-fed rats, whereas liraglutide reduced the levels of miR-27b. In vitro, overexpression of miR-27b decreased the mRNA and protein levels of UCP1, PRDM16, CEBPβ, CIDEA and PGC-1α. Transfection with the miR-27b mimics attenuated the effect of liraglutide on the browning of white adipocytes. Conclusion Liraglutide induced browning of white adipose through regulation of miR-27b.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sara Della Torre ◽  
Valeria Benedusi ◽  
Giovanna Pepe ◽  
Clara Meda ◽  
Nicoletta Rizzi ◽  
...  

AbstractIn female mammals, the cessation of ovarian functions is associated with significant metabolic alterations, weight gain, and increased susceptibility to a number of pathologies associated with ageing. The molecular mechanisms triggering these systemic events are unknown because most tissues are responsive to lowered circulating sex steroids. As it has been demonstrated that isoform alpha of the estrogen receptor (ERα) may be activated by both estrogens and amino acids, we test the metabolic effects of a diet enriched in specific amino acids in ovariectomized (OVX) mice. This diet is able to block the OVX-induced weight gain and fat deposition in the liver. The use of liver-specific ERα KO mice demonstrates that the hepatic ERα, through the control of liver lipid metabolism, has a key role in the systemic response to OVX. The study suggests that the liver ERα might be a valuable target for dietary treatments for the post-menopause.


Marine Drugs ◽  
2021 ◽  
Vol 19 (9) ◽  
pp. 491
Author(s):  
Jesus Valcarcel ◽  
Javier Fraguas ◽  
Carolina Hermida-Merino ◽  
Daniel Hermida-Merino ◽  
Manuel M. Piñeiro ◽  
...  

Rising trends in fish filleting are increasing the amount of processing by-products, such as skins of turbot, a flatfish of high commercial value. In line with circular economy principles, we propose the valorization of turbot skins through a two-step process: initial gelatin extraction described for the first time in turbot, followed by hydrolysis of the remaining solids to produce collagen hydrolysates. We assayed several methods for gelatin extraction, finding differences in gelatin properties depending on chemical treatment and temperature. Of all methods, the application of NaOH, sulfuric, and citric acids at 22 °C results in the highest gel strength (177 g), storage and loss moduli, and gel stability. We found no relation between mechanical properties and content of pyrrolidine amino acids, but the best performing gelatin displays higher structural integrity, with less than 30% of the material below 100 kDa. Collagen hydrolysis was more efficient with papain than alcalase, leading to a greater reduction in Mw of the hydrolysates, which contain a higher proportion of essential amino acids than gelatin and show high in vitro anti-hypertensive activity. These results highlight the suitability of turbot skin by-products as a source of gelatin and the potential of collagen hydrolysates as a functional food and feed ingredient.


2014 ◽  
Vol 44 (2) ◽  
pp. 134-143
Author(s):  
William Renzo Cortez-Vega ◽  
Irene Rodrigues Freitas ◽  
Sandriane Pizato ◽  
Carlos Prentice

Purpose – The purpose of this study was to isolate Whitemouth croaker protein by alkaline solubilization process and evaluate their nutritional quality to evaluate the bioavailability of essential amino acids. Design/methodology/approach – The proximate composition, essential amino acid composition, in vitro digestibility, apparent bioavailability, chemical score of amino acids and SDS-PAGE were determined for the isolated croaker proteins. Findings – The isolated protein showed a high level of protein 92.21 percent and low amount of lipids 0.57 percent. The protein is rich in lysine and leucine, 108.73 and 96.75 mg/g protein, respectively. The protein isolate had high digestibility, 94.32 percent, which indicates proper utilization of this protein source, while the tryptophan had lower bioavailability (12.58 mg amino acid/mg protein). The high chemical scores were found for the amino acids lysine, methionine+cysteine (6.79 and 5.14). SDS-PAGE of proteins extracted showed appearance of the heavy chain of myosin (220 kDa), actin (50 kDa) and other fractions, with molecular weight between 20 and 50 kDa, such as troponin I, C and T. Originality/value – The products obtained from croaker muscle can be incorporated as a high value supplements in human diets. The isolated protein exhibited a high content of essential amino acids and digestibility, indicating that the protein has a high nutritional quality.


Author(s):  
F.I. Vasilevich ◽  
◽  
V.N. Shevkoplyas ◽  
V.M. Bachinskaya ◽  
◽  
...  

The materials on the study of the feed additive Abiotonic in rabbit breeding, as well as the results of organoleptic, microbiological, histological studies and the amino acid composition of rabbit meat of the New Zealand white breed are presented. According to the results of the studies, there was no negative effect of the feed additive on the veterinary and sanitary indicators of rabbit meat, the carcasses were well bled, drying crusts were formed in a timely manner, the muscles were elastic, light pink, white fat, the broth was clear and aromatic. No pathogenic and conditionally pathogenic microflora were found. At the same time, it was noted that the feed additive contributed to the increase in meat of non-essential amino acids by 6,01%, essential amino acids by 9,74%, which increases the biological value of the product. According to histomorphological studies, the Abiotonic feed supplement did not adversely affect the physiological state of animals, muscle tissue and internal organs developed within the physiological norm of rabbits.


Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Guannan Zhou ◽  
Tao Yang ◽  
Sivarajan Kumarasamy ◽  
Bina Joe ◽  
Lauren G Koch

Introduction: Low exercise capacity is a strong predictor of cardiovascular disease and overall mortality. Previously we have shown that rats artificially selected for low intrinsic exercise capacity (LCR) have reduced longevity and develop features consistent with metabolic syndrome (MetS) compared to high intrinsic exercise capacity rats (HCR). Current knowledge suggests that gut microbiota is an important contributor for host fitness. Thus, we hypothesized that transferring gut microbiota from LCR rats into inbred high capacity runner (HCR /Tol ) rats would increase risk factors for MetS, including high blood pressure (BP), gain in body weight (BW), and altered resting energy metabolism. Methods: Gut microbiota was depleted in male HCR/ Tol rats (4 mo.) by an antibiotic cocktail given orally (50mg/kg of BW/day) for 5 days, followed by weekly fecal microbiota transfer (FMT) from male LCR or HCR rats (13 mo.) to generate HCR/ Tol -LCR FMT (n = 5) or HCR/ Tol -HCR FMT (n = 6) groups. BW was measured every 4 weeks. At week 11, whole body metabolism was measured by indirect calorimetry (Oxymax, Columbus Instruments). Respiratory Exchange Ratio (RER), Energy Expenditure (EE), glucose and fat oxidation were calculated from oxygen consumption and carbon dioxide release (VO 2 and VCO 2 ). At week 12, BP was measured by tail-cuff method (Kent Scientific) and treadmill exercise test was done at week 13. Results: Compared to HCR/ Tol -HCR FMT , HCR/ Tol -LCR FMT showed a significant gain in BW (7.2% vs 1.9%, P<0.05), elevated systolic BP (147 vs 120 mmHg, P<0.0001), diastolic BP (112 vs 91 mmHg, P<0.01), and mean BP (123 vs 100 mmHg, P<0.001). BP changes in HCR/ Tol -LCR FMT associated with 1) increased VO 2 (355 vs 320 ml/hr, P<0.05), 2) elevated VCO 2 (350 vs 298 ml/hr, P<0.01), 3) increased EE (1.8 vs 1.6 kcal/hr, P<0.01), 4) higher RER (0.96 vs 0.91, P<0.001), 5) higher glucose oxidation (1.36 vs 1.12 g/kg/hr, P<0.001) and 6) reduced fatty acid oxidation (0.09 vs 0.15 g/kg/hr, P<0.01) and a 23% lower exercise capacity. Conclusions: Gut microbiota from LCR rats strongly associated with poor health outcomes, notably elevated BP and impaired energy metabolism. These findings suggest that altered energy homeostasis by microbiota is mechanistically linked to host BP regulation within MetS.


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