scholarly journals Mercaptoacetate blocks fatty acid-induced GLP-1 secretion in male rats by directly antagonizing GPR40 fatty acid receptors

2016 ◽  
Vol 310 (8) ◽  
pp. R724-R732 ◽  
Author(s):  
Ai-Jun Li ◽  
Qing Wang ◽  
Thu T. Dinh ◽  
Steve M. Simasko ◽  
Sue Ritter
Keyword(s):  
Fatty Acid ◽  
Partial Agonist ◽  
Male Rats ◽  
Alternative Mechanism ◽  
Nodose Ganglion Neurons ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion ◽  
Ganglion Neurons

Mercaptoacetate (MA) is an orexigenic agent reported to block fatty acid (FA) oxidation. Recently, however, we reported evidence from isolated nodose ganglion neurons that MA antagonizes the G protein-coupled long- and medium-chain FA receptor GPR40. GPR40 mediates FA-induced secretion of the satietogenic incretin peptide glucagon-like peptide 1 (GLP-1), by enteroendocrine L cells, as well as FA-induced enhancement of glucose-stimulated insulin secretion. Our results in cultured nodose neurons suggest that MA would also block GPR40 in enteroendocrine cells controlling GLP-1 secretion. If so, this would suggest an alternative mechanism by which MA increases food intake. We tested the hypothesis that MA blocks FA-induced GLP-1 secretion in vitro using cultured STC-1 cells (a murine enteroendocrine cell line) and in vivo in adult male rats. In vitro, MA blocked the increase in both cytosolic Ca2+ and GLP-1 release stimulated by FAs and also reduced (but less effectively) the response of STC-1 cells to grifolic acid, a partial agonist of the GPR120 FA receptor. In vivo, MA reduced GLP-1 secretion following olive oil gavage while also increasing glucose and decreasing insulin levels. The carnitine palmatoyltransferase 1 antagonist etomoxir did not alter these responses. Results indicate that MA's actions, including its orexigenic effect, are mediated by GPR40 (and possibly GPR120) receptor antagonism and not by blockade of fat oxidation, as previously believed. Analysis of MA's interaction with GPR40 may facilitate understanding of the multiple functions of this receptor and the manner in which FAs participate in the control of hunger and satiety.

A moderate increase in carnitine palmitoyltransferase 1a activity is sufficient to substantially reduce hepatic triglyceride levels

2008 ◽  
Vol 294 (5) ◽  
pp. E969-E977 ◽  
Author(s):  
Maja Stefanovic-Racic ◽  
German Perdomo ◽  
Benjamin S. Mantell ◽  
Ian J. Sipula ◽  
Nicholas F. Brown ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Carnitine Palmitoyltransferase ◽  
Male Rats ◽  
Hepatic Insulin Resistance ◽  
Acid Oxidation ◽  
Hepatic Triglyceride

Nonalcoholic fatty liver disease (NAFLD), hypertriglyceridemia, and elevated free fatty acids are present in the majority of patients with metabolic syndrome and type 2 diabetes mellitus and are strongly associated with hepatic insulin resistance. In the current study, we tested the hypothesis that an increased rate of fatty acid oxidation in liver would prevent the potentially harmful effects of fatty acid elevation, including hepatic triglyceride (TG) accumulation and elevated TG secretion. Primary rat hepatocytes were transduced with adenovirus encoding carnitine palmitoyltransferase 1a (Adv-CPT-1a) or control adenoviruses encoding either β-galactosidase (Adv-β-gal) or carnitine palmitoyltransferase 2 (Adv-CPT-2). Overexpression of CPT-1a increased the rate of β-oxidation and ketogenesis by ∼70%, whereas esterification of exogenous fatty acids and de novo lipogenesis were unchanged. Importantly, CPT-1a overexpression was accompanied by a 35% reduction in TG accumulation and a 60% decrease in TG secretion by hepatocytes. There were no changes in secretion of apolipoprotein B (apoB), suggesting the synthesis of smaller, less atherogenic VLDL particles. To evaluate the effect of increasing hepatic CPT-1a activity in vivo, we injected lean or obese male rats with Adv-CPT-1a, Adv-β-gal, or Adv-CPT-2. Hepatic CPT-1a activity was increased by ∼46%, and the rate of fatty acid oxidation was increased by ∼44% in lean and ∼36% in obese CPT-1a-overexpressing animals compared with Adv-CPT-2- or Adv-β-gal-treated rats. Similar to observations in vitro, liver TG content was reduced by ∼37% (lean) and ∼69% (obese) by this in vivo intervention. We conclude that a moderate stimulation of fatty acid oxidation achieved by an increase in CPT-1a activity is sufficient to substantially reduce hepatic TG accumulation both in vitro and in vivo. Therefore, interventions that increase CPT-1a activity could have potential benefits in the treatment of NAFLD.

scholarly journals Free Fatty Acid Induced Reduction in Glucose-Stimulated Insulin Secretion: Evidence for a Role of Oxidative Stress In Vitro and In Vivo

Diabetes ◽  
2007 ◽  
Vol 56 (12) ◽  
pp. 2927-2937 ◽  
Author(s):  
A. I. Oprescu ◽  
G. Bikopoulos ◽  
A. Naassan ◽  
E. M. Allister ◽  
C. Tang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Secretion ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Glucose Stimulated Insulin Secretion

Vagotomy Decreases Excitability in Primary Vagal Afferent Somata

2001 ◽  
Vol 85 (1) ◽  
pp. 247-253 ◽  
Author(s):  
Eric Lancaster ◽  
Eun Joo Oh ◽  
Daniel Weinreich
Keyword(s):  
Vagus Nerve ◽  
Surrounding Tissue ◽  
Membrane Excitability ◽  
Electrophysiological Properties ◽  
Nodose Ganglion Neurons ◽  
Current Steps ◽  
Ganglion Neurons ◽  
Induced Changes

Standard patch-clamp and intracellular recording techniques were used to monitor membrane excitability changes in adult inferior vagal ganglion neurons (nodose ganglion neurons, NGNs) 5 days following section of the vagus nerve (vagotomy). NGNs were maintained in vivo for 5 days following vagotomy, and then in vitro for 2–9 h prior to recording. Vagotomy increased action potential (AP) threshold by over 200% (264 ± 19 pA, mean ± SE, n = 66) compared with control values (81 ± 20 pA, n = 68; P < 0.001). The number of APs evoked by a 3 times threshold 750-ms depolarizing current decreased by >70% (from 8.3 to 2.3 APs, P < 0.001) and the number of APs evoked by a standardized series of (0.1–0.9 nA, 750 ms) depolarizing current steps decreased by over 80% (from 16.9 APs to 2.6 APs, P < 0.001) in vagotomized NGNs. Similar decreases in excitability were observed in vagotomized NGNs in intact ganglia in vitro studied with “sharp” microelectrode techniques. Baseline electrophysiological properties and changes following vagotomy were similar in right and left NGNs. A “sham” vagotomy procedure had no effect on NGN properties at 5 days, indicating that changes were due to severing the vagus nerve itself, not surrounding tissue damage. NGNs isolated after being maintained 17 h in vivo following vagotomy revealed no differences in excitability, suggesting that vagotomy-induced changes occur some time from 1–5 days after injury. Decreased excitability was still observed in NGNs isolated after 20–21 days in vivo following vagotomy. These data indicate that, in contrast to many primary sensory neurons that are thought to become hyperexcitable following section of their axons, NGNs undergo a marked decrease in electrical excitability following vagotomy.

Effects of portacaval shunt and transposition on fatty acid and cholesterol biosynthesis in rat liver

1980 ◽  
Vol 239 (2) ◽  
pp. G83-G89
Author(s):  
J. C. Pector ◽  
J. Winand ◽  
J. P. Dehaye ◽  
J. Christophe
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cholesterol Biosynthesis ◽  
Portacaval Shunt ◽  
Male Rats ◽  
Liver Cholesterol ◽  
Blood Constituents ◽  
Portacaval Transposition

Male rats underwent either portacaval shunt or portacaval transposition; in both cases, sham-operated pair-fed rats served as controls. Three weeks after a portacaval shunt, fasting serum values of glucose (-35%) and cholesterol (-24%) were lower, and fasting plasma glucagon was higher (+65%). The wet weight of the liver and its total content in DNA, RNA, and protein decreased by 43, 40, 43, and 48%, respectively. The supernatant of liver obtained after centrifugation at 700 g incorporated less [1-14C]acetate (-56%) into fatty acids and less [1-14C]acetate (-94%) and [2-14C]mevalonate (-37%) into cholesterol. The activity of acetyl CoA carboxylase was reduced by 56%. The in vivo incorporation of [3H]H2O into liver fatty acids was 83% lower and that into liver cholesterol was 39% lower than in pair-fed controls. Several of the preceding parameters, including in vitro and in vivo labeling of hepatic fatty acids and cholesterol, were found to be mostly normal in rats with portacaval transposition. These data suggest that the reduction of fatty acid and cholesterol biosynthesis in the liver of rats with portacaval shunt was due to the reduction of total hepatic blood flow rather than to the diversion of portal blood constituents.

scholarly journals Stamina-Enhancing Effects of Human Adipose-Derived Stem Cells

2021 ◽  
Vol 30 ◽  
pp. 096368972110354
Author(s):  
Eun-Jung Yoon ◽  
Hye Rim Seong ◽  
Jangbeen Kyung ◽  
Dajeong Kim ◽  
Sangryong Park ◽  
...  
Keyword(s):  
Physical Activity ◽  
Stem Cells ◽  
Locomotor Activity ◽  
Tissue Injury ◽  
Male Rats ◽  
Adipose Derived Stem Cells ◽  
Sprague Dawley ◽  
Serum Triglycerides

Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.

scholarly journals Synthesis, Quantification, and Characterization of Fatty Acid Amides from In Vitro and In Vivo Sources

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2543
Author(s):  
Ruidong Ni ◽  
Suzeeta Bhandari ◽  
Perry R. Mitchell ◽  
Gabriela Suarez ◽  
Neel B. Patel ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Fatty Acid ◽  
Apis Mellifera ◽  
Chemical Synthesis ◽  
Acid Amide ◽  
Fatty Acid Amides ◽  
Fatty Acid Amide

Fatty acid amides are a diverse family of underappreciated, biologically occurring lipids. Herein, the methods for the chemical synthesis and subsequent characterization of specific members of the fatty acid amide family are described. The synthetically prepared fatty acid amides and those obtained commercially are used as standards for the characterization and quantification of the fatty acid amides produced by biological systems, a fatty acid amidome. The fatty acid amidomes from mouse N18TG2 cells, sheep choroid plexus cells, Drosophila melanogaster, Bombyx mori, Apis mellifera, and Tribolium castaneum are presented.

scholarly journals Effect of a Rumen-Protected Microencapsulated Supplement from Linseed Oil on the Growth Performance, Meat Quality, and Fatty Acid Composition in Korean Native Steers

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1253
Author(s):  
Chae-Hyung Sun ◽  
Jae-Sung Lee ◽  
Jalil Ghassemi Nejad ◽  
Won-Seob Kim ◽  
Hong-Gu Lee
Keyword(s):  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Growth Performance ◽  
Meat Quality ◽  
Acid Composition ◽  
Linseed Oil ◽  
Control Group ◽  
Ruminal Fluid

We evaluated the effects of a rumen-protected microencapsulated supplement from linseed oil (MO) on ruminal fluid, growth performance, meat quality, and fatty acid composition in Korean native steers. In an in vitro experiment, ruminal fluid was taken from two fistulated Holstein dairy cows. Different levels of MO (0%, 1%, 2%, 3%, and 4%) were added to the diet. In an in vivo experiment, eight steers (average body weight = 597.1 ± 50.26 kg; average age = 23.8 ± 0.12 months) were assigned to two dietary groups, no MO (control) and MO (3% MO supplementation on a DM basis), for 186 days. The in vitro study revealed that 3% MO is an optimal dose, as there were decreases in the neutral detergent fiber and acid detergent fiber digestibility at 48 h (p < 0.05). The in vivo study showed increases in the feed efficiency and average daily gain in the 3% MO group compared to the control group on days 1 to 90 (p < 0.05). Regarding meat quality, the shear force produced by the longissimus thoracis muscle in steers from the 3% MO group was lower than that produced by the control group (p < 0.05). Interestingly, in terms of the fatty acid profile, higher concentrations of C22:6n3 were demonstrated in the subcutaneous fat and higher concentrations of C18:3n3, C20:3n3, and C20:5n3 were found in the intramuscular fat from steers fed with 3% MO (p < 0.05). Our results indicate that supplementation with 3% MO supplements improves the growth performance and meat quality modulated by the omega-3 fatty acid content of meat in Korean native steers.

Effects of in vivo gonadal hormone environment on in vitro hGRF-40-stimulated GH release

1985 ◽  
Vol 249 (3) ◽  
pp. E276-E280 ◽  
Author(s):  
W. S. Evans ◽  
R. J. Krieg ◽  
E. R. Limber ◽  
D. L. Kaiser ◽  
M. O. Thorner
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Gonadal Hormone ◽  
Base Line ◽  
Pituitary Cells ◽  
Intact Male ◽  
Castrate Male ◽  
Basal Release

The effects of gender and the gonadal hormone environment on basal and stimulated growth hormone (GH) release by dispersed and continuously perifused rat anterior pituitary cells were examined. Cells from intact male and diestrus day 2 female rats and from castrate male rats either untreated or treated with testosterone (T) or 17 beta-estradiol (E2) were used. Basal GH release (ng/min per 10(7) cells; mean +/- SE) by cells from diestrus day 2 female rats was less than by cells from castrate rats treated with T (4.3 +/- 0.6 vs. 11.4 +/- 2.7, respectively; P less than 0.025). No other differences in basal release were detected. Concentration-response relationships were documented between human GH-releasing factor 40 (hGRF-40; 0.03-100 nM given as 2.5-min pulses every 27.5 min) and GH release. Mean (+/- SE) overall GH release (ng/min per 10(7) cells) above base line was greater by cells from intact male rats (496 +/- 92) than by cells from castrate (203 +/- 37.3; P less than 0.0001), castrate and T-treated (348 +/- 52.8; P = 0.008), or castrate and E2-treated (58.1 +/- 6.8; P less than 0.001) male rats or by diestrus day 2 rats (68.6 +/- 9.5; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

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