scholarly journals A tissue-specific increase in lipogenesis in rat brown adipose tissue in hypothyroidism

1988 ◽  
Vol 251 (2) ◽  
pp. 553-557 ◽  
Author(s):  
H S Baht ◽  
E D Saggerson
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Maximum Activity ◽  
Brown Adipocyte ◽  
Glycolytic Flux ◽  
Brown Adipocytes ◽  
White Adipocytes ◽  
Brown Adipose

1. Rats were made hypothyroid by feeding them with propylthiouracil together with a low-iodine diet for 4 weeks. 2. [U-14C]Glucose conversion into fatty acids was substantially enhanced in brown adipocytes isolated from hypothyroid rats. Incorporation of 3H2O into fatty acids in vivo was enhanced in hypothyroidism in interscapular brown fat, but not in epididymal white fat or in liver. Hypothyroidism increased the activities of fatty acid synthase and ATP citrate lyase in brown, but not in white, adipocytes. 3. Glycolytic flux in brown adipocytes, quantified by [3-3H]glucose detritiation, was increased by hypothyroidism. This change was accompanied by increased maximum activity of phosphofructokinase. In white adipocytes a large increase in phosphofructokinase maximum activity was observed in hypothyroidism, but this change was accompanied by only small increases in the rate of glucose detritiation by incubated cells. It is suggested that in the brown adipocyte the overall conversion of glucose into fatty acids is enhanced in thyroid deficiency, but that this change is muted in the white adipocyte, possibly because of limitation of glucose transport. 4. Fatty acid synthesis in brown adipocytes from hypothyroid animals was considerably less sensitive to inhibition by exogenous fatty acids than is the process in cells from euthyroid animals. Consequently, the effect of hypothyroidism to enhance lipogenesis is amplified in the presence of physiological concentrations of fatty acid.

scholarly journals Lipogenesis in rat brown adipocytes. Effects of insulin and noradrenaline, contributions from glucose and lactate as precursors and comparisons with white adipocytes

1988 ◽  
Vol 251 (3) ◽  
pp. 701-709 ◽  
Author(s):  
E D Saggerson ◽  
T W J McAllister ◽  
H S Baht
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Male Rats ◽  
Brown Adipocytes ◽  
Exogenous Fatty Acid ◽  
Fat Depots ◽  
White Adipocytes ◽  
Brown Adipose

1. Brown adipocytes were isolated from the interscapular depot of male rats maintained at approx. 21 degrees C. In some experiments parallel studies were made with white adipocytes from the epididymal depot. 2. Insulin increased and noradrenaline decreased [U-14C]glucose incorporation into fatty acids by brown adipocytes. Brown adipocytes differed from white adipocytes in that exogenous fatty acid (palmitate) substantially decreased fatty acid synthesis from glucose. Both noradrenaline and insulin increased lactate + pyruvate formation by brown adipocytes. Brown adipocytes converted a greater proportion of metabolized glucose into lactate + pyruvate and a smaller proportion into fatty acids than did white adipocytes. 3. In brown adipocytes, when fatty acid synthesis from [U-14C]glucose was decreased by noradrenaline or palmitate, incorporation of 3H2O into fatty acids was also decreased to an extent which would not support proposals for extensive recycling into fatty acid synthesis of acetyl-CoA derived from fatty acid oxidation. 4. In the absence of glucose, [U-14C]lactate was a poor substrate for lipogenesis in brown adipocytes, but its use was facilitated by glucose. When brown adipocytes were incubated with 1 mM-lactate + 5 mM-glucose, lactate-derived carbon generally provided at least 50% of the precursor for fatty acid synthesis. 5. Both insulin and noradrenaline increased [U-14C]glucose conversion into CO2 by brown adipocytes (incubated in the presence of lactate) and, in combination, stimulation of glucose oxidation by these two agents showed synergism. Rates of 14CO2 formation from glucose by brown adipocytes were relatively small compared with maximum rates of oxygen consumption by these cells, suggesting that glucose is unlikely to be a major substrate for thermogenesis. 6. Brown adipocytes from 6-week-old rats had considerably lower maximum rates of fatty acid synthesis, relative to cell DNA content, than white adipocytes. By contrast, rates of fatty acid synthesis from 3H2O in vivo were similar in the interscapular and epididymal fat depots. Expressed relative to activities of fatty acid synthase or ATP citrate lyase, however, brown adipocytes synthesized fatty acids as effectively as did white adipocytes. It is suggested that the cells most active in fatty acid synthesis in the brown adipose tissue are not recovered fully in the adipocyte fraction during cell isolation. Differences in rates of fatty acid synthesis between brown and white adipocytes were less apparent at 10 weeks of age.

scholarly journals Lipid Droplets in Brown Adipose Tissue Are Dispensable for Cold-Induced Thermogenesis

2020 ◽  
Author(s):  
Chandramohan Chitraju ◽  
Alexander Fischer ◽  
Robert V. Farese ◽  
Tobias C. Walther
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Lipid Droplets ◽  
Metabolic Energy ◽  
Brown Adipocyte ◽  
Glucose Disposal ◽  
Brown Adipocytes ◽  
Brown Adipose

SUMMARYBrown adipocytes store metabolic energy as triglycerides (TG) in multilocular lipid droplets (LDs). Fatty acids released from brown adipocyte LDs by lipolysis are thought to activate and fuel UCP1-mediated thermogenesis. Here we test this hypothesis by preventing fatty acid storage in murine brown adipocytes through brown adipose tissue (BAT)-specific deletions of the TG synthesis enzymes, DGAT1 and DGAT2 (BA-DGAT KO). Despite the absence of LDs, BA-DGAT KO mice had functional BAT and maintained euthermia during acute or chronic cold exposure. As apparent adaptations to the lack of TG, brown adipocytes of BA-DGAT KO mice appear to utilize circulating glucose and fatty acids, as well as stored glycogen to fuel thermogenesis. Moreover, BA-DGAT KO mice were resistant to diet-induced glucose intolerance, likely due to increased glucose disposal by BAT. Thus, surprisingly, TGs in BAT are dispensable for its function, in part through adaptations to utilize other fuel sources.

scholarly journals Fatty Acid Synthesis Is Essential for Survival of Cryptococcus neoformans and a Potential Fungicidal Target

2007 ◽  
Vol 51 (10) ◽  
pp. 3537-3545 ◽  
Author(s):  
Methee Chayakulkeeree ◽  
Thomas H. Rude ◽  
Dena L. Toffaletti ◽  
John R. Perfect
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cryptococcus Neoformans ◽  
Fatty Acid Synthase ◽  
Acid Synthesis ◽  
Yeast Cells ◽  
Synthase Inhibitor ◽  
The Brain

ABSTRACT Fatty acid synthase in the yeast Cryptococcus neoformans is composed of two subunits encoded by FAS1 and FAS2 genes. We inserted a copper-regulated promoter (P CTR4-2 ) to regulate FAS1 and FAS2 expression in Cryptococcus neoformans (strains P CTR4-2 /FAS1 and P CTR4-2 /FAS2, respectively). Both mutants showed growth rates similar to those of the wild type in a low-copper medium in which FAS1 and FAS2 were expressed, but even in the presence of exogenous fatty acids, strains were suppressed in growth under high-copper conditions. The treatment of C. neoformans with fluconazole was shown to have an increased inhibitory activity and even became fungicidal when either FAS1 or FAS2 expression was suppressed. Furthermore, a subinhibitory dose of fluconazole showed anticryptococcal activity in vitro in the presence of cerulenin, a fatty acid synthase inhibitor. In a murine model of pulmonary cryptococcosis, a tissue census of yeast cells in P CTR4-2 /FAS2 strain at day 7 of infection was significantly lower than that in mice treated with tetrathiomolybdate, a copper chelator (P < 0.05), and a yeast census of P CTR4-2 /FAS1 strain at day 14 of infection in the brain was lower in the presence of more copper. In fact, no positive cultures from the brain were detected in mice (with or without tetrathiomolybdate treatment) infected with the P CTR4-2 /FAS2 strain, which implies that this mutant did not reach the brain in mice. We conclude that both FAS1 and FAS2 in C. neoformans are essential for in vitro and in vivo growth in conditions with and without exogenous fatty acids and that FAS1 and FAS2 can potentially be fungicidal targets for C. neoformans with a potential for synergistic behavior with azoles.

scholarly journals Comparison of triacylglycerol synthesis in rat brown and white adipocytes. Effects of hypothyroidism and streptozotocin-diabetes on enzyme activities and metabolic fluxes

1988 ◽  
Vol 250 (2) ◽  
pp. 325-333 ◽  
Author(s):  
H S Baht ◽  
E D Saggerson
Keyword(s):  
Fatty Acid ◽  
Enzyme Activities ◽  
Metabolic Flux ◽  
Streptozotocin Diabetes ◽  
Fatty Acyl ◽  
Brown Adipocyte ◽  
Acid Oxidation ◽  
Brown Adipocytes ◽  
Triacylglycerol Synthesis ◽  
White Adipocytes

1. Adipocytes were isolated from the interscapular brown fat and the epididymal white fat of normal, streptozotocin-diabetic and hypothyroid rats. 2. Measurements were made of the maximum rate of triacylglycerol synthesis by monitoring the incorporation of [U-14C]glucose into acylglycerol glycerol in the presence of palmitate (1 mM) and insulin (4 nM) and of the activities of the following triacylglycerol-synthesizing enzymes: fatty acyl-CoA synthetase (FAS), mitochondrial and microsomal forms of glycerolphosphate acyltransferase (GPAT), dihydroxyacetonephosphate acyltransferase (DHAPAT), monoacylglycerol phosphate acyltransferase (MGPAT), Mg2+-dependent phosphatidate phosphohydrolase (PPH) and diacylglycerol acyltransferase (DGAT). 3. FAS activity in brown adipocytes was predominantly localized in the mitochondrial fraction, whereas a microsomal localization of this enzyme predominated in white adipocytes. Subcellular distributions of the other enzyme activities in brown adipocytes were similar to those shown previously with white adipocytes [Saggerson, Carpenter, Cheng & Sooranna (1980) Biochem. J. 190, 183-189]. 4. Relative to cell DNA, brown adipocytes had lower activities of triacylglycerol-synthesizing enzymes and showed lower rates of metabolic flux into acylglycerols than did white adipocytes isolated from the same animals. 5. Diabetes decreased both metabolic flux into acylglycerols and the activities of triacylglycerol-synthesizing enzymes in white adipocytes. By contrast, although diabetes decreased metabolic flux into brown-adipocyte acylglycerols by 80%, there were no decreases in the activities of triacylglycerol-synthesizing enzymes, and the activity of PPH was significantly increased. 6. Hypothyroidism increased metabolic flux into acylglycerols in both cell types, and increased activities of all triacylglycerol-synthesizing enzymes in brown adipocytes. By contrast, in white adipocytes, although hypothyroidism increased the activities of FAS, microsomal GPAT and DGAT, this condition decreased the activities of mitochondrial GPAT and PPH. 7. It was calculated that the maximum capabilities for fatty acid oxidation and esterification are approximately equal in brown adipocytes. In white adipocytes esterification is predominant by approx. 100-fold. 8. Diabetes almost abolished incorporation of [U-14C]glucose into fatty acids in both adipocyte types. Hypothyroidism increased fatty acid synthesis in white and brown adipocytes by 50% and 1000% respectively.

Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes

2000 ◽  
Vol 279 (3) ◽  
pp. C670-C681 ◽  
Author(s):  
J. Himms-Hagen ◽  
A. Melnyk ◽  
M. C. Zingaretti ◽  
E. Ceresi ◽  
G. Barbatelli ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Protein ◽  
Protein Composition ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
White Adipocytes ◽  
Bat Mitochondria ◽  
Adrenoceptor Agonist ◽  
Brown Adipose ◽  
A Cell

Multilocular, mitochondria-rich adipocytes appear in white adipose tissue (WAT) of rats treated with the β3-adrenoceptor agonist, CL-316243 (CL). Objectives were to determine whether these multilocular adipocytes derived from cells that already existed in the WAT or from proliferation of precursor cells and whether new mitochondria contained in them were typical brown adipocyte mitochondria. Use of 5-bromodeoxyuridine to identify cells that had undergone mitosis during the CL treatment showed that most multilocular cells derived from cells already present in the WAT. Morphological techniques showed that at least a subpopulation of unilocular adipocytes underwent conversion to multilocular mitochondria-rich adipocytes. A small proportion of multilocular adipocytes (∼8%) was positive for UCP1 by immunohistochemistry. Biochemical techniques showed that mitochondrial protein recovered from WAT increased 10-fold and protein isolated from brown adipose tissue (BAT) doubled in CL-treated rats. Stained gels showed a different protein composition of new mitochondria isolated from WAT from that of mitochondria isolated from BAT. Western blotting showed new mitochondria in WAT to contain both UCP1, but at a much lower concentration than in BAT mitochondria, and UCP3, at a higher concentration than that in BAT mitochondria. We hypothesize that multilocular adipocytes present at 7 days of CL treatment have two origins. First, most come from convertible unilocular adipocytes that become multilocular and make many mitochondria that contain UCP3. Second, some come from a cell that gives rise to more typical brown adipocytes that express UCP1.

Uptake of glucose and release of fatty acids and glycerol by rat brown adipose tissue in vivo

1986 ◽  
Vol 64 (5) ◽  
pp. 609-614 ◽  
Author(s):  
Stephanie W. Y. Ma ◽  
David O. Foster
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Tissue Blood Flow ◽  
Glycerol Release ◽  
Maximal Stimulation ◽  
Brown Adipose ◽  
Lactate And Pyruvate

The net in vivo uptake or release of free fatty acids glycerol, glucose, lactate, and pyruvate by the interscapular brown adipose tissue (IBAT) of barbital-anesthetized, cold-acclimated rats was determined from measurements of plasma arteriovenous concentration differences across IBAT and tissue blood flow. Measurements were made without stimulation of the tissue and also during submaximal and maximal stimulation by infused noradrenaline (NA), the physiological activator of BAT thermogenesis. There was no appreciable uptake of glucose or release of fatty acids and glycerol by the nonstimulated tissue. At both levels of stimulation there was significant uptake of glucose (1.7 and 2.0 μmol/min) and release of glycerol (0.9 and 1.2 μmol/min), but only at maximal stimulation was there significant release of fatty acids (1.9 μmol/min). Release of lactate and pyruvate accounted for 33% of the glucose taken up at submaximal stimulation and 88% at maximal stimulation. By calculation, the remainder of the glucose taken up was sufficient to have fueled about 12% of the thermogenesis at submaximal stimulation, but only about 2% at maximal stimulation. As estimated from the rate of glycerol release, the rate of triglyceride hydrolysis was sufficient at submaximal stimulation to fuel IBAT thermogenesis entirely with the resulting fatty acids, but it was not sufficient to do so at maximal stimulation when some of the fatty acid was exported. It is suggested that at maximal NA-induced thermogenesis a portion of lipolysis proceeded only to the level of mono- and di-glycerides with the result that glycerol release did not fully reflect the rate of fatty acid formation. Both in absolute terms and in relation to the export of glycerol the in vivo export of fatty acids from the adipocytes of IBAT was much less than is observed with brown adipocytes in vitro.

scholarly journals Dietary Coleus Amboinicus Herb Decreases Ruminal Methanogenesis and Biohydrogenation, and Improves Meat Quality and Fatty Acid Composition in Longissimus Thoracis of Lambs

2021 ◽  
Author(s):  
Yulianri Rizki Yanza ◽  
Malgorzata Szumacher-Strabel ◽  
Dorota Lechniak ◽  
Sylwester Ślusarczyk ◽  
Pawel Kolodziejski ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Meat Quality ◽  
Methane Production ◽  
Fatty Acid Synthase ◽  
Unsaturated Fatty Acids ◽  
Biologically Active ◽  
Coleus Amboinicus

Abstract Background: This study aimed to investigate the effect of biologically active compounds (BAC) of Coleus amboinicus Lour. (CAL) herb fed to growing lambs on ruminal methane production, ruminal biohydrogenation of unsaturated fatty acids and meat characteristics. An in vitro trial (Experiment 1) comprising of control and three experimental diets (CAL constituting 10%, 15%, and 20% of the total diet) was conducted to determine an effective dose for in vivo experiments. After the in vitro trial, two in vivo experiments were conducted on six growing, rumen-cannulated lambs (Experiment 2) and 16 growing lambs (Experiment 3), which were assigned into the control (CON) and one experimental diet (20% of CAL). Several parameters were examined in vitro (pH, ammonia and VFA concentrations, protozoa, methanogens and select bacteria populations) and in vivo (methane production, digestibility, ruminal microorganism populations, meat quality, fatty acids profiles in rumen fluid and meat, transcript expression of 5 genes in meat). Results: The CAL lowered in vitro methane production by 51%. In the in vivo experiments, lambs fed CAL decreased methane production by 20% compared with the CON animals (Experiment 3), which corresponded to the reduced total methanogens counts in all experiments up to 28%, notably Methanobacteriales. In Experiment 3, CAL increased or tended to increase the numbers of Ruminococcus albus, Megasphaeraelsdenii, Butyrivibrioproteoclasticus, and Butyrivibriofibrisolvens. Dietary CAL suppressed the Holotricha population, but increased or tended to increase Entodiniomorpha population in Experiments 2 and 3. An increase in the polyunsaturated fatty acid (PUFA) proportion in the rumen of lambs was noted in response to the CAL diet, which was mainly attributable to the increase in C18:3 cis-9 cis-12 cis-15 (LNA) proportion. The CAL reduced the mRNA expressions of four investigated genes in meat (fatty acid synthase, stearoyl-CoA desaturase, lipoprotein lipase, and fatty acid desaturase 1). Conclusions:Summarizing, polyphenols of CAL (20% in diet) origin can mitigate ruminal methane production by inhibiting the methanogens communities. Supplementation of CAL also provides favorable conditions in the rumen by modulating ruminal bacteria involved in fermentation and biohydrogenation of fatty acids. CAL elevated the LNA concentration, which led to improved meat quality through increased deposition of n-3 PUFA.

scholarly journals Identification and characterization of distinct brown adipocyte subtypes in C57BL/6J mice

2020 ◽  
Vol 4 (1) ◽  
pp. e202000924
Author(s):  
Ruth Karlina ◽  
Dominik Lutter ◽  
Viktorian Miok ◽  
David Fischer ◽  
Irem Altun ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Expression Profiles ◽  
Stromal Vascular Fraction ◽  
Gene Expression Profiles ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Brown Adipose

Brown adipose tissue (BAT) plays an important role in the regulation of body weight and glucose homeostasis. Although increasing evidence supports white adipose tissue heterogeneity, little is known about heterogeneity within murine BAT. Recently, UCP1 high and low expressing brown adipocytes were identified, but a developmental origin of these subtypes has not been studied. To obtain more insights into brown preadipocyte heterogeneity, we use single-cell RNA sequencing of the BAT stromal vascular fraction of C57/BL6 mice and characterize brown preadipocyte and adipocyte clonal cell lines. Statistical analysis of gene expression profiles from brown preadipocyte and adipocyte clones identify markers distinguishing brown adipocyte subtypes. We confirm the presence of distinct brown adipocyte populations in vivo using the markers EIF5, TCF25, and BIN1. We also demonstrate that loss of Bin1 enhances UCP1 expression and mitochondrial respiration, suggesting that BIN1 marks dormant brown adipocytes. The existence of multiple brown adipocyte subtypes suggests distinct functional properties of BAT depending on its cellular composition, with potentially distinct functions in thermogenesis and the regulation of whole body energy homeostasis.

scholarly journals Regulation of rat foetal lipogenesis in brown adipose tissue in vivo and in isolated brown adipocytes during the last day of, and after prolonged, gestation

1987 ◽  
Vol 243 (2) ◽  
pp. 617-620 ◽  
Author(s):  
C Roncero ◽  
M Lorenzo ◽  
M Benito
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Incubation Medium ◽  
Brown Adipocyte ◽  
Isolated Cells ◽  
Pregnant Rats ◽  
Brown Adipocytes ◽  
Brown Adipose

Rates of lipogenesis in foetal isolated brown adipocytes from 22-day-pregnant rats were significantly increased by lactate plus pyruvate as major substrates in the incubation medium, in comparison with the endogenous rates. Insulin stimulated foetal brown-adipocyte lipogenesis, and adrenaline or noradrenaline and isoprenaline decreased lipogenesis. Glucagon had no effect on the lipogenic rate in brown adipocytes. Progesterone administration to the mother significantly increased the rates of lipogenesis in brown adipose tissue and in isolated brown adipocytes from 22-day foetuses. Prolongation of gestation by progesterone to day 23 decreased the rates of brown-adipose-tissue lipogenesis in vivo and in isolated cells in the post-mature foetuses.

Two functional FAS-I type fatty acid synthases in Corynebacterium glutamicum

Microbiology ◽  
2005 ◽  
Vol 151 (7) ◽  
pp. 2421-2427 ◽  
Author(s):  
Eva Radmacher ◽  
Luke J. Alderwick ◽  
Gurdyal S. Besra ◽  
Alistair K. Brown ◽  
Kevin J. C. Gibson ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Corynebacterium Glutamicum ◽  
Fatty Acid Synthase ◽  
Lipid Analysis ◽  
Growth Yield ◽  
Mycolic Acid ◽  
Mycolic Acids ◽  
Fatty Acid Synthases

The lipid-rich Corynebacterianeae, to which Corynebacterium glutamicum and Mycobacterium species belong, produce both fatty acids and mycolic acids. Compared with most other bacteria, C. glutamicum possesses two fatty acid synthases, encoded by fasA (8907 kb; FAS-IA) and fasB (8988 kb; FAS-IB). Here, it was shown by mutational analyses that fasA is essential but fasB is not. However, in a fasA background, the fasB mutation results in a slightly reduced growth yield, l-glutamate production is increased, and comparative lipid analysis suggests that in vivo FAS-IB is active primarily to supply palmitate. Transcript quantifications revealed that the fasB transcript contributes 32 % to both fas transcripts during growth on glucose, affirmative for fasB expression, and that fasB is subordinate to fasA. The fasA transcript is downregulated by 8·3-fold during growth on acetate as compared with glucose. The lipid analyses also demonstrate that cells grown on propionate produce a number of uneven fatty acids (e.g. 15 : 0, 17 : 0, 17 : 1), which are not present in cells grown on glucose or acetate, suggesting that fatty acid synthase in vivo may also use propionyl-CoA as the priming unit in fatty acid synthesis. The fatty acid auxotrophic fasAB double mutant was used to determine the suggested incorporation of fatty acids into mycolic acids. Supplementation of this mutant with uniformly labelled [13C]oleate and analysis of isolated mycolic acids confirmed that mature mycolic acids in the mutant consist exclusively of two fused [13C]oleate molecules. In addition to an altered phospholipid profile, the fasB mutant also exhibits differences in its mycolic acid profile. Taken together, the results show that although FAS-IA is the most relevant fatty acid synthase of C. glutamicum and FAS-IB is supplementary, both synthases are necessary to produce the characteristic lipid environment of this organism.

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