scholarly journals Impact of Branched Chain Amino Acid Supplementation on Adipose Tissue Lipolysis

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 496-496
Author(s):  
Tabitha Gregory ◽  
Chaitra Surugihalli ◽  
Vaishna Muralidaran ◽  
Marilyn Fisher ◽  
Nishanth Sunny

Abstract Objectives Branched chain amino acids (BCAAs), Valine, Leucine, and Isoleucine have been shown to impact adipose tissue physiology through regulation of adipocyte differentiation, lipogenesis, and lipolysis. Further, circulating BCAAs are elevated during obesity and insulin resistance, a characteristic attributed to impaired BCAA catabolic networks in adipose tissue and skeletal muscle. The objective of this study was to determine whether the induction of lipolysis in adipose tissue is a characteristic feature prompted by the chronic availability of BCAAs. Methods Mice (C57-BL6N) were kept on low-fat (LF, 10% fat calories; n = 9) and low-fat supplemented with 150% BCAA (LB; n = 10) diets for 34 weeks. Following an overnight fast (∼12–14 hrs),  serum and perigonadal adipose (PGA) tissue samples were collected for metabolic analysis. Serum free fatty acids (FFAs) were analyzed and 25 milligrams (mg) of PGA was used for an in vitro lipolysis assay. Lipolysis in the PGA was induced under basal and isoproterenol (ISP, 10 micromolar, μM) stimulated conditions for 2 hours. In a second experiment, PGA tissue explants from normal mice (n = 18) were incubated with two levels of BCAA supplementation (500 μM and 1 millimolar, mM). FFAs in the incubation media were measured as an index of adipose tissue lipolysis. Results Overnight fasting body weights of the LF and LB mice remained similar. However, PGA tissue weights were significantly lower in the LB group (grams ± SEM; LF, 1.34 ± 0.09 vs LB, 0.84 ± 0.11, P = 0.003). LB serum FFAs were elevated (mM FFAs ± SEM; LF 0.73 ± 0.04 vs LB, 0.88 ± 0.04, P = 0.01). Basal lipolysis (mM FFAs/mg tissue protein ± SEM) trended to be higher in the PGA from the LB animals (LF, 1.44 ± 0.18 vs LB, 1.88 ± 0.15, P = 0.08). While ISP significantly induced lipolysis, the stimulated lipolytic rates remained similar between LF and LB groups. When normal PGA explants were challenged with BCAAs, the 1mM BCAA supplemented group tended to show higher fatty acid release (mM FFAs/mg tissue protein ± SEM; 500 μM, 0.89 ± 0.06 vs 1mM,  1.02 ± 0.05,  P = 0.09). Conclusions In summary, these results suggest that BCAA mediated increases in adipose tissue lipolysis can contribute to circulating FFA levels. BCAA mediated lipolysis and the subsequent increase in circulating FFAs could indirectly modulate substrate oxidation in peripheral tissues including liver and muscle. Funding Sources NIH RO1

2020 ◽  
Vol 98 (2) ◽  
pp. 85-92 ◽  
Author(s):  
Mihaela Ionica ◽  
Oana M. Aburel ◽  
Adrian Vaduva ◽  
Alexandra Petrus ◽  
Sonia Rațiu ◽  
...  

Obesity is an age-independent, lifestyle-triggered, pandemic disease associated with both endothelial and visceral adipose tissue (VAT) dysfunction leading to cardiometabolic complications mediated via increased oxidative stress and persistent chronic inflammation. The purpose of the present study was to assess the oxidative stress in VAT and vascular samples and the effect of in vitro administration of vitamin D. VAT and mesenteric artery branches were harvested during abdominal surgery performed on patients referred for general surgery (n = 30) that were randomized into two subgroups: nonobese and obese. Serum levels of C-reactive protein (CRP) and vitamin D were measured. Tissue samples were treated or not with the active form of vitamin D: 1,25(OH)2D3 (100 nmol/L, 12 h). The main findings are that in obese patients, (i) a low vitamin D status was associated with increased inflammatory markers and reactive oxygen species generation in VAT and vascular samples and (ii) in vitro incubation with vitamin D alleviated oxidative stress in VAT and vascular preparations and also improved the vascular function. We report here that the serum level of vitamin D is inversely correlated with the magnitude of oxidative stress in the adipose tissue. Ex vivo treatment with active vitamin D mitigated obesity-related oxidative stress.


2015 ◽  
Vol 58 (1) ◽  
pp. 159-163 ◽  
Author(s):  
K. F. Schiller ◽  
S. Preuss ◽  
S. Kaffarnik ◽  
W. Vetter ◽  
M. Rodehutscord ◽  
...  

Abstract. Intense sheep odour and flavour in lamb is often associated with lower consumer acceptance. Branched-chain fatty acids (BCFAs) are suggested as possible reasons. Therefore, muscle and subcutaneous adipose tissue samples of 98 lamb chops were analysed for three BCFAs (4-methyloctanoic, 4-ethyloctanoic and 4-methylnonanoic fatty acid). Samples were derived from a previous study, in which lambs were raised and fattened under intensive conditions and tested for sensory quality. BCFA contents of fat extracts from muscle tissue were very low and quantification was not possible. In subcutaneous adipose tissue different concentrations of BCFA and differences between crosses were detected. The sex of lambs had a significant influence. The BCFA correlations were significant, while correlations between BCFA of adipose tissue and sensory traits were not significant. Therefore, it seems likely that BCFA concentrations were too low and/or other substances are involved in causing the lamb flavour detected through sensory analysis.


2001 ◽  
Vol 170 (2) ◽  
pp. 425-431 ◽  
Author(s):  
C Menendez ◽  
M Lage ◽  
R Peino ◽  
R Baldelli ◽  
P Concheiro ◽  
...  

Leptin, the product of the ob gene, is secreted into the circulation by white adipose tissue; its major role being to participate in the regulation of energy homeostasis. Plasma leptin levels are mainly determined by the relative adiposity of the subject; however, the great dispersion of values for any given body mass index and the noteworthy gender-based differences indicate that other factors are operating. Steroid hormones actively participate in the regulation of leptin secretion; however, non-steroid nuclear hormones have either not been studied or have provided contradictory results. In order to understand the role of hormones of the non-steroid superfamily such as 3,5,3'-tri-iodothyronine (T(3)), vitamin D(3) and retinoic acid (RA) in the control of leptin secretion, in the present work doses of 10(-9), 10(-8) and 10(-7) M of these compounds have been studied on in vitro leptin secretion. The organ culture was performed with omental adipose tissue samples from healthy donors (n=28). T(3) was devoid of effect at any dose studied, while an inhibition of leptin secretion was observed with 9-cis-RA (slight) and all-trans-RA (potent). Interestingly, vitamin D(3) exerted a powerfully inhibitory role at the doses studied, and its action was synergistic with all-trans-RA. In conclusion, in vitro leptin secretion by human adipose tissue is negatively controlled by either RA or vitamin D(3). The clinical significance of leptin regulation by this superfamily of nuclear receptors remains to be ascertained.


1992 ◽  
Vol 263 (4) ◽  
pp. R857-R862 ◽  
Author(s):  
R. H. Migliorini ◽  
J. S. Lima-Verde ◽  
C. R. Machado ◽  
G. M. Cardona ◽  
M. A. Garofalo ◽  
...  

Lipolytic activity of fish (Hoplias malabaricus), toad (Bufo paracnemis), and snake (Philodryas patagoniensis) adipose tissue was investigated in vivo and in vitro. Catecholamines or glucagon did not affect the release of free fatty acids (FFA) by incubated fish and toad adipose tissue. Catecholamines also failed to activate snake adipose tissue lipolysis, which even decreased in the presence of epinephrine. However, glucagon stimulated both the lipolytic activity of reptilian tissue in vitro and the mobilization of FFA to plasma when administered to snakes in vivo. The release of FFA from incubated fish, amphibian, and reptilian adipose tissue increased markedly in the presence of cAMP or xanthine derivatives, inhibitors of phosphodiesterase. Forskolin or fluoride, activators of specific components of the adenylate cyclase system, strongly stimulated toad adipose tissue lipolysis. The data suggest that adipocyte triacylglycerol lipase of ectotherm vertebrates is activated by a cAMP-mediated phosphorylation and that the organization of the membrane-bound adenylate cyclase system is similar to that of mammals.


1997 ◽  
Vol 152 (3) ◽  
pp. 465-475 ◽  
Author(s):  
K L Houseknecht ◽  
D E Bauman

To investigate the cellular mechanisms of somatotropin (ST) action on adipose tissue lipolysis, experiments were conducted using adipose tissue taken from lactating cows treated with excipient or ST (40 mg/day). Stimulation of lipolysis in vitro by the effectors isoproterenol with or without adenosine deaminase, dibutyryl cAMP with or without isobutylmethylxanthine, and forskolin was not altered by ST treatment. Conversely, the response to the antilipolytic effector, phenylisopropyladenosine (PIA), was significantly reduced in adipose tissue explants from ST or fasted cows. The different responses to adrenergic-stimulating agents (in vivo) and PIA (in vitro) were not due to differences in the abundance of α, β or γ subunits of the stimulatory (Gs) and inhibitory (Gi) subunits of the heterotrimeric G-proteins which bind to the β-adrenergic and adenosine receptors respectively. However, the functionality of Gi proteins, as assessed by their ability to be ADP-ribosylated by pertussis toxin, was significantly reduced in ST-treated but not fasted cows. These data highlight differential regulation of signaling proteins by ST and fasting, both of which result in enhanced in vivo response to adrenergic stimulation of lipolysis. Journal of Endocrinology (1997) 152, 465–475


Oncogene ◽  
2021 ◽  
Author(s):  
Yulin Zhang ◽  
Yang Kong ◽  
Yuan Ma ◽  
Shilei Ni ◽  
Tobias Wikerholmen ◽  
...  

AbstractDysregulated iron metabolism is a hallmark of many cancers, including glioblastoma (GBM). However, its role in tumor progression remains unclear. Herein, we identified coatomer protein complex subunit zeta 1 (COPZ1) as a therapeutic target candidate which significantly dysregulated iron metabolism in GBM cells. Overexpression of COPZ1 was associated with increasing tumor grade and poor prognosis in glioma patients based on analysis of expression data from the publicly available database The Cancer Genome Atlas (P < 0.001). Protein levels of COPZ1 were significantly increased in GBM compared to non-neoplastic brain tissue samples in immunohistochemistry and western blot analysis. SiRNA knockdown of COPZ1 suppressed proliferation of U87MG, U251 and P3#GBM in vitro. Stable expression of a COPZ1 shRNA construct in U87MG inhibited tumor growth in vivo by ~60% relative to controls at day 21 after implantation (P < 0.001). Kaplan–Meier analysis of the survival data demonstrated that the overall survival of tumor bearing animals increased from 20.8 days (control) to 27.8 days (knockdown, P < 0.05). COPZ1 knockdown also led to the increase in nuclear receptor coactivator 4 (NCOA4), resulting in the degradation of ferritin, and a subsequent increase in the intracellular levels of ferrous iron and ultimately ferroptosis. These data demonstrate that COPZ1 is a critical mediator in iron metabolism. The COPZ1/NCOA4/FTH1 axis is therefore a novel therapeutic target for the treatment of human GBM.


1987 ◽  
Vol 252 (1) ◽  
pp. E85-E95 ◽  
Author(s):  
H. J. Mersmann

A pig model in vivo was used to confirm the unique specificity for stimulation of porcine adipose tissue lipolysis by norepinephrine analogues in vitro. Plasma free fatty acid and blood glycerol concentrations were monitored as probable indicators of adipose tissue lipolysis. Plasma glucose and lactate concentrations, blood pressure, and heart rate were monitored also. Norepinephrine analogues were infused intravenously. Several compounds, classified as either beta 1- or beta 2-adrenergic agonists, that stimulated lipolysis in vitro also increased plasma free fatty acid and blood glycerol concentrations in vivo. Tazolol (beta 1) and quinterenol (beta 2) did not stimulate lipolysis in vitro and likewise did not elevate plasma free fatty acid or blood glycerol concentrations in vivo. Clenbuterol and zinterol did not stimulate lipolysis in vitro but elevated plasma free fatty acid concentrations in vivo, implying indirect effects. Isoproterenol stimulation of plasma free fatty acid and blood glycerol concentrations in vivo was antagonized by propranolol, implying the beta-adrenergic nature of the receptors. Infusion of purported beta 1- and beta 2-adrenergic antagonists suggested control of lipolysis in vivo predominantly by beta 1-adrenergic receptors; however, because the results in vitro do not indicate this specificity, differential pharmacodynamics of the antagonists are suggested rather than designation of receptor subtypes. There was no evidence for alpha-adrenergic mediated inhibition of adipose tissue lipolysis in vivo, confirming observations in vitro.


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