scholarly journals Emerging Roles for Serotonin in Regulating Metabolism: New Implications for an Ancient Molecule

2019 ◽  
Vol 40 (4) ◽  
pp. 1092-1107 ◽  
Author(s):  
Julian M Yabut ◽  
Justin D Crane ◽  
Alexander E Green ◽  
Damien J Keating ◽  
Waliul I Khan ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Drug Targets ◽  
Energy Homeostasis ◽  
De Novo ◽  
Nutrient Absorption ◽  
The Body ◽  
De Novo Lipogenesis ◽  
Nonalcoholic Fatty Liver ◽  
Multiple Organs ◽  
Brown Adipose

Abstract Serotonin is a phylogenetically ancient biogenic amine that has played an integral role in maintaining energy homeostasis for billions of years. In mammals, serotonin produced within the central nervous system regulates behavior, suppresses appetite, and promotes energy expenditure by increasing sympathetic drive to brown adipose tissue. In addition to these central circuits, emerging evidence also suggests an important role for peripheral serotonin as a factor that enhances nutrient absorption and storage. Specifically, glucose and fatty acids stimulate the release of serotonin from the duodenum, promoting gut peristalsis and nutrient absorption. Serotonin also enters the bloodstream and interacts with multiple organs, priming the body for energy storage by promoting insulin secretion and de novo lipogenesis in the liver and white adipose tissue, while reducing lipolysis and the metabolic activity of brown and beige adipose tissue. Collectively, peripheral serotonin acts as an endocrine factor to promote the efficient storage of energy by upregulating lipid anabolism. Pharmacological inhibition of serotonin synthesis or signaling in key metabolic tissues are potential drug targets for obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD).

scholarly journals Hepatic ANGPTL3 regulates adipose tissue energy homeostasis

2015 ◽  
Vol 112 (37) ◽  
pp. 11630-11635 ◽  
Author(s):  
Yan Wang ◽  
Markey C. McNutt ◽  
Serena Banfi ◽  
Michael G. Levin ◽  
William L. Holland ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
De Novo ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
De Novo Lipogenesis ◽  
Fed State ◽  
Beneficial Effects ◽  
Brown Adipose

Angiopoietin-like protein 3 (ANGPTL3) is a circulating inhibitor of lipoprotein and endothelial lipase whose physiological function has remained obscure. Here we show that ANGPTL3 plays a major role in promoting uptake of circulating very low density lipoprotein-triglycerides (VLDL-TGs) into white adipose tissue (WAT) rather than oxidative tissues (skeletal muscle, heart brown adipose tissue) in the fed state. This conclusion emerged from studies of Angptl3−/− mice. Whereas feeding increased VLDL-TG uptake into WAT eightfold in wild-type mice, no increase occurred in fed Angptl3−/− animals. Despite the reduction in delivery to and retention of TG in WAT, fat mass was largely preserved by a compensatory increase in de novo lipogenesis in Angptl3−/− mice. Glucose uptake into WAT was increased 10-fold in KO mice, and tracer studies revealed increased conversion of glucose to fatty acids in WAT but not liver. It is likely that the increased uptake of glucose into WAT explains the increased insulin sensitivity associated with inactivation of ANGPTL3. The beneficial effects of ANGPTL3 deficiency on both glucose and lipoprotein metabolism make it an attractive therapeutic target.

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.

scholarly journals Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states

2010 ◽  
Vol 299 (3) ◽  
pp. R728-R739 ◽  
Author(s):  
Barbara E. Hasek ◽  
Laura K. Stewart ◽  
Tara M. Henagan ◽  
Anik Boudreau ◽  
Natalie R. Lenard ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
De Novo ◽  
Uncoupling Protein ◽  
Nutrient Sensing ◽  
De Novo Lipogenesis ◽  
Endocrine Function ◽  
Fischer 344 ◽  
Methionine Restriction ◽  
Heat Increment

Dietary methionine restriction (MR) is a mimetic of chronic dietary restriction (DR) in the sense that MR increases rodent longevity, but without food restriction. We report here that MR also persistently increases total energy expenditure (EE) and limits fat deposition despite increasing weight-specific food consumption. In Fischer 344 (F344) rats consuming control or MR diets for 3, 9, and 20 mo, mean EE was 1.5-fold higher in MR vs. control rats, primarily due to higher EE during the night at all ages. The day-to-night transition produced a twofold higher heat increment of feeding (3.0°C vs. 1.5°C) in MR vs. controls and an exaggerated increase in respiratory quotient (RQ) to values greater than 1, indicative of the interconversion of glucose to lipid by de novo lipogenesis. The simultaneous inhibition of glucose utilization and shift to fat oxidation during the day was also more complete in MR (RQ ∼0.75) vs. controls (RQ ∼0.85). Dietary MR produced a rapid and persistent increase in uncoupling protein 1 expression in brown (BAT) and white adipose tissue (WAT) in conjunction with decreased leptin and increased adiponectin levels in serum, suggesting that remodeling of the metabolic and endocrine function of adipose tissue may have an important role in the overall increase in EE. We conclude that the hyperphagic response to dietary MR is matched to a coordinated increase in uncoupled respiration, suggesting the engagement of a nutrient-sensing mechanism, which compensates for limited methionine through integrated effects on energy homeostasis.

scholarly journals Association of genes with physiological functions by comparative analysis of pooled expression microarray data

2013 ◽  
Vol 45 (2) ◽  
pp. 69-78 ◽  
Author(s):  
Iuan-bor D. Chen ◽  
Vinay K. Rathi ◽  
Diana S. DeAndrade ◽  
Patrick Y. Jay
Keyword(s):  
Transcription Factor ◽  
Adipose Tissue ◽  
Regulatory Element ◽  
The Body ◽  
Accurate Identification ◽  
Physiological Functions ◽  
Microarray Expression Data ◽  
Multiple Organs ◽  
Brown Adipose ◽  
Sterol Regulatory Element

The physiological functions of a tissue in the body are carried out by its complement of expressed genes. Genes that execute a particular function should be more specifically expressed in tissues that perform the function. Given this premise, we mined public microarray expression data to build a database of genes ranked by their specificity of expression in multiple organs. The database permitted the accurate identification of genes and functions known to be specific to individual organs. Next, we used the database to predict transcriptional regulators of brown adipose tissue (BAT) and validated two candidate genes. Based upon hypotheses regarding pathways shared between combinations of BAT or white adipose tissue (WAT) and other organs, we identified genes that met threshold criteria for specific or counterspecific expression in each tissue. By contrasting WAT to the heart and BAT, the two most mitochondria-rich tissues in the body, we discovered a novel function for the transcription factor ESRRG in the induction of BAT genes in white adipocytes. Because the heart and other estrogen-related receptor gamma (ESRRG)-rich tissues do not express BAT markers, we hypothesized that an adipocyte co-regulator acts with ESRRG. By comparing WAT and BAT to the heart, brain, kidney and skeletal muscle, we discovered that an isoform of the transcription factor sterol regulatory element binding transcription factor 1 (SREBF1) induces BAT markers in C2C12 myocytes in the presence of ESRRG. The results demonstrate a straightforward bioinformatic strategy to associate genes with functions. The database upon which the strategy is based is provided so that investigators can perform their own screens.

scholarly journals Sex Differences in Brown Adipose Tissue Function: Sex Hormones, Glucocorticoids, and Their Crosstalk

2021 ◽  
Vol 12 ◽  
Author(s):  
Kasiphak Kaikaew ◽  
Aldo Grefhorst ◽  
Jenny A. Visser
Keyword(s):  
Sex Differences ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Sex Hormones ◽  
Energy Homeostasis ◽  
Overweight And Obesity ◽  
The Body ◽  
Bat Activity ◽  
Pathological Conditions ◽  
Brown Adipose

Excessive fat accumulation in the body causes overweight and obesity. To date, research has confirmed that there are two types of adipose tissue with opposing functions: lipid-storing white adipose tissue (WAT) and lipid-burning brown adipose tissue (BAT). After the rediscovery of the presence of metabolically active BAT in adults, BAT has received increasing attention especially since activation of BAT is considered a promising way to combat obesity and associated comorbidities. It has become clear that energy homeostasis differs between the sexes, which has a significant impact on the development of pathological conditions such as type 2 diabetes. Sex differences in BAT activity may contribute to this and, therefore, it is important to address the underlying mechanisms that contribute to sex differences in BAT activity. In this review, we discuss the role of sex hormones in the regulation of BAT activity under physiological and some pathological conditions. Given the increasing number of studies suggesting a crosstalk between sex hormones and the hypothalamic-pituitary-adrenal axis in metabolism, we also discuss this crosstalk in relation to sex differences in BAT activity.

scholarly journals Advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Laura Pajed ◽  
Ulrike Taschler ◽  
Anna Tilp ◽  
Peter Hofer ◽  
Petra Kotzbeck ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Liver ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
De Novo ◽  
Lipolytic Activity ◽  
De Novo Lipogenesis ◽  
Hormone Sensitive Lipase ◽  
Hepatic Lipid Accumulation ◽  
Hormone Sensitive

AbstractModulation of adipocyte lipolysis represents an attractive approach to treat metabolic diseases. Lipolysis mainly depends on two enzymes: adipose triglyceride lipase and hormone-sensitive lipase (HSL). Here, we investigated the short- and long-term impact of adipocyte HSL on energy homeostasis using adipocyte-specific HSL knockout (AHKO) mice. AHKO mice fed high-fat-diet (HFD) progressively developed lipodystrophy accompanied by excessive hepatic lipid accumulation. The increased hepatic triglyceride deposition was due to induced de novo lipogenesis driven by increased fatty acid release from adipose tissue during refeeding related to defective insulin signaling in adipose tissue. Remarkably, the fatty liver of HFD-fed AHKO mice reversed with advanced age. The reversal of fatty liver coincided with a pronounced lipodystrophic phenotype leading to blunted lipolytic activity in adipose tissue. Overall, we demonstrate that impaired adipocyte HSL-mediated lipolysis affects systemic energy homeostasis in AHKO mice, whereby with older age, these mice reverse their fatty liver despite advanced lipodystrophy.

scholarly journals Regulation and Metabolic Significance of De Novo Lipogenesis in Adipose Tissues

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1383 ◽  
Author(s):  
Ziyi Song ◽  
Alus Xiaoli ◽  
Fajun Yang
Keyword(s):  
Energy Homeostasis ◽  
De Novo ◽  
Current Knowledge ◽  
De Novo Lipogenesis ◽  
Adipose Tissues ◽  
Brown Adipose ◽  
Therapeutic Opportunity ◽  
Regulate Energy Metabolism

De novo lipogenesis (DNL) is a complex and highly regulated process in which carbohydrates from circulation are converted into fatty acids that are then used for synthesizing either triglycerides or other lipid molecules. Dysregulation of DNL contributes to human diseases such as obesity, type 2 diabetes, and cardiovascular diseases. Thus, the lipogenic pathway may provide a new therapeutic opportunity for combating various pathological conditions that are associated with dysregulated lipid metabolism. Hepatic DNL has been well documented, but lipogenesis in adipocytes and its contribution to energy homeostasis and insulin sensitivity are less studied. Recent reports have gained significant insights into the signaling pathways that regulate lipogenic transcription factors and the role of DNL in adipose tissues. In this review, we will update the current knowledge of DNL in white and brown adipose tissues with the focus on transcriptional, post-translational, and central regulation of DNL. We will also summarize the recent findings of adipocyte DNL as a source of some signaling molecules that critically regulate energy metabolism.

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 Anti-Obesity Effects of Microalgae

2019 ◽  
Vol 21 (1) ◽  
pp. 41 ◽  
Author(s):  
Saioa Gómez-Zorita ◽  
Jenifer Trepiana ◽  
Maitane González-Arceo ◽  
Leixuri Aguirre ◽  
Iñaki Milton-Laskibar ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
In Vivo Studies ◽  
Acid Oxidation ◽  
Low Grade ◽  
Food Ingredients ◽  
Brown Adipose

In recent years, microalgae have attracted great interest for their potential applications in nutraceutical and pharmaceutical industry as an interesting source of bioactive medicinal products and food ingredients with anti-oxidant, anti-inflammatory, anti-cancer, and anti-microbial properties. One potential application for bioactive microalgae compounds is obesity treatment. This review gathers together in vitro and in vivo studies which address the anti-obesity effects of microalgae extracts. The scientific literature supplies evidence supporting an anti-obesity effect of several microalgae: Euglena gracilis, Phaeodactylum tricornutum, Spirulina maxima, Spirulina platensis, or Nitzschia laevis. Regarding the mechanisms of action, microalgae can inhibit pre-adipocyte differentiation and reduce de novo lipogenesis and triglyceride (TG) assembly, thus limiting TG accumulation. Increased lipolysis and fatty acid oxidation can also be observed. Finally, microalgae can induce increased energy expenditure via thermogenesis activation in brown adipose tissue, and browning in white adipose tissue. Along with the reduction in body fat accumulation, other hallmarks of individuals with obesity, such as enhanced plasma lipid levels, insulin resistance, diabetes, or systemic low-grade inflammation are also improved by microalgae treatment. Not only the anti-obesity effect of microalgae but also the improvement of several comorbidities, previously observed in preclinical studies, has been confirmed in clinical trials.

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