scholarly journals Circadian lipid synthesis in brown fat maintains murine body temperature during chronic cold

2019 ◽  
Vol 116 (37) ◽  
pp. 18691-18699 ◽  
Author(s):  
Marine Adlanmerini ◽  
Bryce J. Carpenter ◽  
Jarrett R. Remsberg ◽  
Yann Aubert ◽  
Lindsey C. Peed ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Body Temperature ◽  
Cold Exposure ◽  
De Novo ◽  
Lipid Synthesis ◽  
Acid Synthesis ◽  
High Amplitude ◽  
De Novo Lipogenesis ◽  
Brown Adipose ◽  
The Impact

Ambient temperature influences the molecular clock and lipid metabolism, but the impact of chronic cold exposure on circadian lipid metabolism in thermogenic brown adipose tissue (BAT) has not been studied. Here we show that during chronic cold exposure (1 wk at 4 °C), genes controlling de novo lipogenesis (DNL) includingSrebp1, the master transcriptional regulator of DNL, acquired high-amplitude circadian rhythms in thermogenic BAT. These conditions activated mechanistic target of rapamycin 1 (mTORC1), an inducer ofSrebp1expression, and engaged circadian transcriptional repressors REV-ERBα and β as rhythmic regulators ofSrebp1in BAT. SREBP was required in BAT for the thermogenic response to norepinephrine, and depletion of SREBP prevented maintenance of body temperature both during circadian cycles as well as during fasting of chronically cold mice. By contrast, deletion of REV-ERBα and β in BAT allowed mice to maintain their body temperature in chronic cold. Thus, the environmental challenge of prolonged noncircadian exposure to cold temperature induces circadian induction of SREBP1 that drives fuel synthesis in BAT and is necessary to maintain circadian body temperature during chronic cold exposure. The requirement for BAT fatty acid synthesis has broad implications for adaptation to cold.

scholarly journals Maternal cold exposure induces distinct transcriptome changes in the placenta and fetal brown adipose tissue in mice

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sujoy Ghosh ◽  
Chul-Hong Park ◽  
Jisu Lee ◽  
Nathan Lee ◽  
Rui Zhang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Temperature Adaptation ◽  
Myosin Filament ◽  
Expression Of Genes ◽  
Brown Adipose ◽  
The Impact

Abstract Background Brown adipose tissue (BAT) is specialized to dissipate energy in the form of heat. BAT-mediated heat production in rodents and humans is critical for effective temperature adaptation of newborns to the extrauterine environment immediately after birth. However, very little is known about whether and how fetal BAT development is modulated in-utero in response to changes in maternal thermal environment during pregnancy. Using BL6 mice, we evaluated the impact of different maternal environmental temperatures (28 °C and 18 °C) on the transcriptome of the placenta and fetal BAT to test if maternal cold exposure influences fetal BAT development via placental remodeling. Results Maternal weight gain during pregnancy, the average number of fetuses per pregnancy, and placental weight did not differ between the groups at 28 °C and 18 °C. However, the average fetal weight at E18.5 was 6% lower in the 18 °C-group compared to the 28 °C-group. In fetal BATs, cold exposure during pregnancy induced increased expression of genes involved in de novo lipogenesis and lipid metabolism while decreasing the expression of genes associated with muscle cell differentiation, thus suggesting that maternal cold exposure may promote fetal brown adipogenesis by suppressing the myogenic lineage in bidirectional progenitors. In placental tissues, maternal cold exposure was associated with upregulation of genes involved in complement activation and downregulation of genes related to muscle contraction and actin-myosin filament sliding. These changes may coordinate placental adaptation to maternal cold exposure, potentially by protecting against cold stress-induced inflammatory damage and modulating the vascular and extravascular contractile system in the placenta. Conclusions These findings provide evidence that environmental cold temperature sensed by the mother can modulate the transcriptome of placental and fetal BAT tissues. The ramifications of the observed gene expression changes warrant future investigation.

scholarly journals Central Resistin Regulates Hypothalamic and Peripheral Lipid Metabolism in a Nutritional-Dependent Fashion

Endocrinology ◽  
2008 ◽  
Vol 149 (9) ◽  
pp. 4534-4543 ◽  
Author(s):  
María J. Vázquez ◽  
C. Ruth González ◽  
Luis Varela ◽  
Ricardo Lage ◽  
Sulay Tovar ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Mrna Expression ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Acid Synthesis ◽  
Inhibitory Effect ◽  
De Novo Lipogenesis ◽  
Dependent Manner ◽  
Fed State

Evidence suggests that the adipocyte-derived hormone resistin (RSTN) directly regulates both feeding and peripheral metabolism through, so far, undefined hypothalamic-mediated mechanisms. Here, we demonstrate that the anorectic effect of RSTN is associated with inappropriately decreased mRNA expression of orexigenic (agouti-related protein and neuropeptide Y) and increased mRNA expression of anorexigenic (cocaine and amphetamine-regulated transcript) neuropeptides in the arcuate nucleus of the hypothalamus. Of interest, RSTN also exerts a profound nutrition-dependent inhibitory effect on hypothalamic fatty acid metabolism, as indicated by increased phosphorylation levels of both AMP-activated protein kinase and its downstream target acetyl-coenzyme A carboxylase, associated with decreased expression of fatty acid synthase in the ventromedial nucleus of the hypothalamus. In addition, we also demonstrate that chronic central RSTN infusion results in decreased body weight and major changes in peripheral expression of lipogenic enzymes, in a tissue-specific and nutrition-dependent manner. Thus, in the fed state central RSTN is associated with induced expression of fatty acid synthesis enzymes and proinflammatory cytokines in liver, whereas its administration in the fasted state does so in white adipose tissue. Overall, our results indicate that RSTN controls feeding and peripheral lipid metabolism and suggest that hepatic RSTN-induced insulin resistance may be mediated by central activation of de novo lipogenesis in liver.

Development of lipogenesis and insulin sensitivity in tissues of the ob/ob mouse

1981 ◽  
Vol 240 (2) ◽  
pp. E101-E107 ◽  
Author(s):  
M. L. Kaplan ◽  
G. A. Leveille
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Glycogen Synthesis ◽  
Lipid Synthesis ◽  
Acid Synthesis ◽  
De Novo Lipogenesis ◽  
Glycerophosphate Dehydrogenase

Lipogenesis and insulin sensitivity are evaluated in adipose tissue, liver, and diaphragm of ob/ob and non-ob/ob mice. In ob/ob mice, hepatic fatty acid synthesis from [U-14C]glucose is elevated by 4 wk of age, and adipose tissue fatty acid synthesis increases at approximately 7 wk. Hepatic activities in ob/ob mice of glucose-6-phosphate dehydrogenase (EC 1.1.1.49), 6-phosphogluconate dehydrogenase (EC 1.1.1.44), malate dehydrogenase (EC 1.1.1.40), and alpha-glycerophosphate dehydrogenase (EC 1.1.1.8) are dramatically increased by 7 wk of age. Diminished insulin-stimulated glycogen synthesis is first noted in the diaphragm of ob/ob mice at 7 wk of age. Insulin-stimulated glycogen synthesis in adipose tissue of ob/ob mice is impaired at 3 wk. At 7 wk, insulin-stimulated fatty acid synthesis in adipose tissue of ob/ob mice is markedly increased. Adipose tissue glyceride-glycerol synthesis continues to increase throughout development, whereas fatty acid synthesis decreases after 7 wk. The data suggest that alterations in lipid synthesis occur very early in the development of ob/ob mouse, prior to expression to overt obesity, at which time a major contribution to lipogenesis is made by the liver. The altered de novo lipogenesis does not precede the reported diminution in energy metabolism.

scholarly journals Physical Activity Reduces Anxiety And Regulates Brain Fatty Acid Synthesis

2020 ◽  
Author(s):  
Arkadiusz Damian Liśkiewicz ◽  
Marta Przybyła ◽  
Anna Wojakowska ◽  
Łukasz Marczak ◽  
Katarzyna Bogus ◽  
...  
Keyword(s):  
Physical Activity ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Lipid Synthesis ◽  
Tca Cycle ◽  
Acid Synthesis ◽  
De Novo Lipogenesis ◽  
Brain Functions ◽  
The Brain

Abstract Physical activity impacts brain functions, but the direct mechanisms of this effect are not fully recognized or understood. Among multidimensional changes induced by physical activity, brain fatty acids (FA) appear to play an important role; however, the knowledge in this area is particularly scarce. Here we performed global metabolomics profiling of the hippocampus and the frontal cortex (FC) in a model of voluntary running in mice. Examined brain structures responded differentially to physical activity. Specifically, the markers of the tricarboxylic acid (TCA) cycle were downregulated in the FC, whereas glycolysis was enhanced in the hippocampus. Physical activity stimulated production of myristic, palmitic and stearic FA; i.e., the primary end products of de novo lipogenesis in the brain, which was accompanied by increased expression of hippocampal fatty acid synthase (FAS), suggesting stimulation of lipid synthesis. The changes in the brain fatty acid profile were associated with reduced anxiety level in the running mice. Overall, the study examines exercise-related metabolic changes in the brain and links them to behavioral outcomes.

Activation of the farnesoid X receptor improves lipid metabolism in combined hyperlipidemic hamsters

2006 ◽  
Vol 290 (4) ◽  
pp. E716-E722 ◽  
Author(s):  
Stefan Bilz ◽  
Varman Samuel ◽  
Katsutaro Morino ◽  
David Savage ◽  
Cheol Soo Choi ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Plasma Concentrations ◽  
Farnesoid X Receptor ◽  
De Novo Lipogenesis ◽  
Plasma Triglycerides ◽  
The Metabolic Syndrome ◽  
High Fructose ◽  
The Impact

The transcription factor farnesoid X receptor (FXR) has recently been implicated in the control of hepatic triglyceride production. Activation of FXR may ameliorate hypertriglyceridemia, a cardinal feature of the metabolic syndrome. Because hamsters share many characteristic features of human lipid metabolism, we used a high-fructose-fed hamster model to study the impact of FXR activation with chenodeoxycholic acid (CDCA) on plasma lipoprotein metabolism. Male Syrian hamsters fed a diet containing 60% kcal from fructose for 2 wk developed hypertriglyceridemia and hypercholesterolemia (+120 and +60%, P = 0.005 and 0.0004 vs. controls) due to increased hepatic lipoprotein production. This could be largely attributed to enhanced hepatic de novo lipogenesis, as indicated by increased expression of sterol regulatory element-binding protein-1, fatty acid synthase, and steaoryl-CoA desaturase-1. Lipoprotein analysis demonstrated that the increase in plasma triglycerides occurred in the VLDL density range, whereas increases in VLDL, IDL/LDL, and HDL cholesterol accounted for the elevated plasma cholesterol concentrations. Addition of 0.1% CDCA to the high-fructose diet decreased hepatic de novo lipogenesis and consequently triglyceride production and prevented the increases in plasma triglycerides and cholesterol (−40 and −18%, P = 0.03 and 0.03 vs. high fructose-fed animals). CDCA-treated animals had lower VLDL triglycerides and decreased VLDL and IDL/LDL cholesterol plasma concentrations. These data demonstrate that activation of FXR with CDCA effectively lowers plasma triglyceride and cholesterol concentrations, mainly by decreasing de novo lipogenesis and hepatic secretion of triglyceride-rich lipoproteins. Our studies identify activators of FXR as promising new tools in the therapy of hypertriglyceridemic states, including the insulin resistance syndrome and type 2 diabetes.

scholarly journals Physical Activity Reduces Anxiety And Regulates Brain Fatty Acid Synthesis

2020 ◽  
Author(s):  
Arkadiusz Damian Liśkiewicz ◽  
Marta Przybyła ◽  
Anna Wojakowska ◽  
Łukasz Marczak ◽  
Katarzyna Bogus ◽  
...  
Keyword(s):  
Physical Activity ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Lipid Synthesis ◽  
Tca Cycle ◽  
Acid Synthesis ◽  
De Novo Lipogenesis ◽  
Brain Functions ◽  
The Brain

Abstract Physical activity impacts brain functions, but the direct mechanisms of this effect are not fully recognized or understood. Among multidimensional changes induced by physical activity, brain fatty acids (FA) appear to play an important role; however, the knowledge in this area is particularly scarce. Here we performed global metabolomics profiling of the hippocampus and the frontal cortex (FC) in a model of voluntary running in mice. Examined brain structures responded differentially to physical activity. Specifically, the markers of the tricarboxylic acid (TCA) cycle were downregulated in the FC, whereas glycolysis was enhanced in the hippocampus. Physical activity stimulated production of myristic, palmitic and stearic FA; i.e., the primary end products of de novo lipogenesis in the brain, which was accompanied by increased expression of hippocampal fatty acid synthase (FAS), suggesting stimulation of lipid synthesis. The changes in the brain fatty acid profile were associated with reduced anxiety level in the running mice. Overall, the study examines exercise-related metabolic changes in the brain and links them to behavioral outcomes.

scholarly journals Kinetic Analysis of Lipid Metabolism in Live Breast Cancer Cells via Nonlinear Optical Microscopy

2019 ◽  
Author(s):  
J. Hou ◽  
N. E. Reid ◽  
B. J. Tromberg ◽  
E. O. Potma
Keyword(s):  
Breast Cancer ◽  
Lipid Metabolism ◽  
Optical Microscopy ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
De Novo ◽  
Lipid Synthesis ◽  
Acid Synthesis ◽  
Live Cells ◽  
Consumption Rates

AbstractInvestigating the behavior of breast cancer cells via reaction kinetics may help unravel the mechanisms that underlie metabolic changes in tumors. However, obtaining human in vivo kinetic data is challenging due to difficulties associated with measuring these parameters. Non-destructive methods of measuring lipid content in live cells, provide a novel approach to quantitatively model lipid synthesis and consumption. In this study, two-photon excited fluorescence (TPEF) was used to determine metabolic rates via the cell’s optical redox ratio (ORR) as reported by fluorescence intensity ratios of metabolic coenzymes, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD+). Concurrently, coherent Raman scattering (CRS) microscopy was used to probe de novo intracellular lipid content. Combining non-linear optical microscopy and Michaelis-Menten-kinetics based simulations, we isolated fatty acid synthesis/consumption rates and elucidated effects of altered lipid metabolism in T47D breast cancer cells. When treated with 17β-Estradiol (E2), cancer cells showed a 3-fold increase in beta-oxidation rate as well as a 50% increase in cell proliferation rate. Similarly, the rate of de novo lipid synthesis in cancer cells treated with E2 was increased by 60%. Furthermore, we treated T47D cells with etomoxir (ETO) and observed that cancer cells treated with ETO exhibited a ∼70% reduction in β-oxidation. These results show the ability to probe lipid alterations in live cells with minimum interruption, to characterize both glucose and lipid metabolism in breast cancer cells via quantitative kinetic models and parameters.Statement of SignificanceCombining non-linear optical microscopy (NLOM) and deuterium labeling provides insight into lipid metabolism in live cancer cells during cancer development and progression. The dynamic metabolic data is modelled with Michaelis-Menten-kinetics to independently quantify the lipid synthesis and utilization in cancer cells. Changes in lipid levels are found to originate from de novo lipid synthesis using glucose as a source, lipid consumption from β-oxidation and lipid consumption from cell proliferation, processes that can separately analyzed with the Michaelis-Menten model. In this work, we isolate fatty acid synthesis/consumption rates and elucidated effects of altered lipid metabolism in T47D breast cancer cells in response to estradiol stimulation and etomoxir treatment, dynamic processes that cannot be easily observed without the application of appropriate models.

scholarly journals Lipid Metabolism Is Dysregulated before, during and after Pregnancy in a Mouse Model of Gestational Diabetes

2021 ◽  
Vol 22 (14) ◽  
pp. 7452
Author(s):  
Samuel Furse ◽  
Denise S. Fernandez-Twinn ◽  
Davide Chiarugi ◽  
Albert Koulman ◽  
Susan E. Ozanne
Keyword(s):  
Lipid Metabolism ◽  
Gestational Diabetes ◽  
Glucose Tolerance ◽  
Mouse Model ◽  
Time Course ◽  
De Novo ◽  
Lipid Analysis ◽  
Temporal Distribution ◽  
De Novo Lipogenesis ◽  
Analysis Tool

The aim of the current study was to test the hypothesis that maternal lipid metabolism was modulated during normal pregnancy and that these modulations are altered in gestational diabetes mellitus (GDM). We tested this hypothesis using an established mouse model of diet-induced obesity with pregnancy-associated loss of glucose tolerance and a novel lipid analysis tool, Lipid Traffic Analysis, that uses the temporal distribution of lipids to identify differences in the control of lipid metabolism through a time course. Our results suggest that the start of pregnancy is associated with several changes in lipid metabolism, including fewer variables associated with de novo lipogenesis and fewer PUFA-containing lipids in the circulation. Several of the changes in lipid metabolism in healthy pregnancies were less apparent or occurred later in dams who developed GDM. Some changes in maternal lipid metabolism in the obese-GDM group were so late as to only occur as the control dams’ systems began to switch back towards the non-pregnant state. These results demonstrate that lipid metabolism is modulated in healthy pregnancy and the timing of these changes is altered in GDM pregnancies. These findings raise important questions about how lipid metabolism contributes to changes in metabolism during healthy pregnancies. Furthermore, as alterations in the lipidome are present before the loss of glucose tolerance, they could contribute to the development of GDM mechanistically.

Effect of carbohydrate intake on de novo lipogenesis in human adipose tissue

1987 ◽  
Vol 253 (6) ◽  
pp. E664-E669 ◽  
Author(s):  
C. Chascione ◽  
D. H. Elwyn ◽  
M. Davila ◽  
K. M. Gil ◽  
J. Askanazi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
De Novo ◽  
Acid Synthesis ◽  
De Novo Lipogenesis ◽  
Whole Body ◽  
High Intake ◽  
Carbohydrate Diet ◽  
Triglyceride Synthesis ◽  
High Carbohydrate

Rates of synthesis, from [14C]glucose, of fatty acids (de novo lipogenesis) and glycerol (triglyceride synthesis) were measured in biopsies of adipose tissue from nutritionally depleted patients given low- or high-carbohydrate intravenous nutrition. Simultaneously, energy expenditure and whole-body lipogenesis were measured by indirect calorimetry. Rates of whole-body lipogenesis were zero on the low-carbohydrate diet and averaged 1.6 g.kg-1.day-1 on the high-carbohydrate diet. In vitro rates of triglyceride synthesis increased 3-fold going from the low to the high intake; rates of fatty acid synthesis increased approximately 80-fold. In vitro, lipogenesis accounted for less than 0.1% of triglyceride synthesis on the low intake and 4% on the high intake. On the high-carbohydrate intake, in vitro rates of triglyceride synthesis accounted for 61% of the rates of unidirectional triglyceride synthesis measured by indirect calorimetry. In vitro rates of lipogenesis accounted for 7% of whole-body lipogenesis. Discrepancies between in vitro rates of fatty acid synthesis from glucose, compared with acetate and citrate, as reported by others, suggest that in depleted patients on hypercaloric high-carbohydrate diets, adipose tissue may account for up to 40% of whole-body lipogenesis.

scholarly journals Metabolic Effects of Oral Phenelzine Treatment on High-Sucrose-Drinking Mice

2018 ◽  
Vol 19 (10) ◽  
pp. 2904 ◽  
Author(s):  
Christian Carpéné ◽  
Saioa Gómez-Zorita ◽  
Alice Chaplin ◽  
Josep Mercader
Keyword(s):  
Adipose Tissue ◽  
Phosphoenolpyruvate Carboxykinase ◽  
De Novo ◽  
Uncoupling Protein ◽  
De Novo Lipogenesis ◽  
Metabolic Effects ◽  
Mrna Levels ◽  
Brown Adipose ◽  
High Sucrose ◽  
Sucrose Drinking

Phenelzine has been suggested to have an antiobesity effect by inhibiting de novo lipogenesis, which led us to investigate the metabolic effects of oral chronic phenelzine treatment in high-sucrose-drinking mice. Sucrose-drinking mice presented higher body weight gain and adiposity versus controls. Phenelzine addition did not decrease such parameters, even though fat pad lipid content and weights were not different from controls. In visceral adipocytes, phenelzine did not impair insulin-stimulated de novo lipogenesis and had no effect on lipolysis. However, phenelzine reduced the mRNA levels of glucose transporters 1 and 4 and phosphoenolpyruvate carboxykinase in inguinal white adipose tissue (iWAT), and altered circulating levels of free fatty acids (FFA) and glycerol. Interestingly, glycemia was restored in phenelzine-treated mice, which also had higher insulinaemia. Phenelzine-treated mice presented higher rectal temperature, which was associated to reduced mRNA levels of uncoupling protein 1 in brown adipose tissue. Furthermore, unlike sucrose-drinking mice, hepatic malondialdehyde levels were not altered. In conclusion, although de novo lipogenesis was not inhibited by phenelzine, the data suggest that the ability to re-esterify FFA is impaired in iWAT. Moreover, the effects on glucose homeostasis and oxidative stress suggest that phenelzine could alleviate obesity-related alterations and deserves further investigation in obesity models.

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