Wnt/Wingless signaling promotes lipid mobilization through signal-induced transcriptional repression.

The Wnt/Wingless signaling pathway plays critical roles in metazoan development and energy metabolism, but its role in regulating lipid homeostasis remains not fully understood. Here, we report that the activation of canonical Wnt/Wg signaling promotes lipolysis while concurrently inhibiting lipogenesis and fatty acid ß-oxidation in both larval and adult adipocytes, as well as cultured S2R+ cells, in Drosophila. Using RNA-sequencing and CUT&RUN (Cleavage Under Targets & Release Using Nuclease) assays, we identified a set of Wnt target genes responsible for intracellular lipid homeostasis. Notably, active Wnt signaling directly represses the transcription of these genes, resulting in decreased de novo lipogenesis and fatty acid ß-oxidation, but increased lipolysis. These changes lead to elevated free fatty acids and reduced triglyceride (TG) accumulation in adipocytes with active Wnt signaling. Conversely, downregulation of Wnt signaling in the fat body promotes TG accumulation in both larval and adult adipocytes. The attenuation of Wnt signaling also increases the expression of specific lipid metabolism-related genes in larval adipocytes, wing discs, and adult intestines. Taken together, these findings suggest that Wnt signaling-induced transcriptional repression plays an important role in regulating lipid homeostasis by enhancing lipolysis while simultaneously suppressing lipogenesis and fatty acid ß-oxidation.

Time-restricted eating affects human adipose tissue fat mobilization.

OBJECTIVE: Time-restricted eating (TRE), a dietary approach that confines food intake to specific time windows, has shown metabolic benefits. However, its impact on body weight loss remains inconclusive. The objective of this study was to investigate the influence of early TRE (eTRE) and delayed TRE (dTRE) on fat mobilization using human adipose tissue (AT) cultures. METHODS: Subcutaneous AT was collected from 21 participants with severe obesity. We assessed fat mobilization by measuring glycerol release in AT culture across four treatment conditions: control, eTRE, dTRE, and 24-h fasting. RESULTS: TRE had a significant impact on lipolysis (glycerol release [mean (SD)] in micromoles per hour per gram: control, 0.05 [0.003]; eTRE, 0.10 [0.006]; dTRE, 0.08 [0.005]; and fasting, 0.17 [0.008]; p < 0.0001). Both eTRE and dTRE increased lipolysis compared with the control group, with eTRE showing higher glycerol mobilization than dTRE during the overall 24-h time window, especially at the nighttime/habitual sleep episode (p < 0.0001). Further analysis of TRE based on fasting duration revealed that, independently of the time window, glycerol release increased with fasting duration (in micromoles per hour per gram: 8 h = 0.08 [0.001]; 12 h = 0.09 [0.008]; and 16 h of fasting = 0.12 [0.011]; p < 0.0001). CONCLUSIONS: This study provides insights into the potential benefits of TRE on fat mobilization and may guide the design of future dietary strategies for weight management and metabolic health.

Transcriptional determinants of lipid mobilization in human adipocytes.

Defects in adipocyte lipolysis drive multiple aspects of cardiometabolic disease, but the transcriptional framework controlling this process has not been established. To address this, we performed a targeted perturbation screen in primary human adipocytes. Our analyses identified 37 transcriptional regulators of lipid mobilization, which we classified as (i) transcription factors, (ii) histone chaperones, and (iii) mRNA processing proteins. On the basis of its strong relationship with multiple readouts of lipolysis in patient samples, we performed mechanistic studies on one hit, ZNF189, which encodes the zinc finger protein 189. Using mass spectrometry and chromatin profiling techniques, we show that ZNF189 interacts with the tripartite motif family member TRIM28 and represses the transcription of an adipocyte-specific isoform of phosphodiesterase 1B (PDE1B2). The regulation of lipid mobilization by ZNF189 requires PDE1B2, and the overexpression of PDE1B2 is sufficient to attenuate hormone-stimulated lipolysis. Thus, our work identifies the ZNF189-PDE1B2 axis as a determinant of human adipocyte lipolysis and highlights a link between chromatin architecture and lipid mobilization.

Follistatin-like 1 is a myokine regulating lipid mobilization during endurance exercise and recovery.

OBJECTIVE: The aim of this study was to investigate the role of the follistatin-like 1 (Fstl1) and disco-interacting protein 2 homolog A (DIP2a) axis in relation to lipid metabolism during and after endurance exercise and to elucidate the mechanisms underlying the metabolic effects of Fstl1 on adipocytes, considering its regulation by exercise and muscle mass and its link to obesity. METHODS: Twenty-nine sedentary males participated in endurance exercise, and blood samples were collected during and after the exercise. Body composition, Fstl1, glycerol, epinephrine, growth hormone, and atrial natriuretic peptide were measured. 3T3-L1 adipocytes, with or without DIP2a knockdown, were treated with Fstl1 to assess glycerol release, cyclic AMP/cyclic GMP production, and hormone sensitive lipase phosphorylation. The association between DIP2a gene expression levels in human adipose tissues and exercise-induced lipolysis was examined. RESULTS: Fstl1 levels significantly increased during endurance exercise and following recovery, correlating with lean body mass and lipolysis. In 3T3-L1 adipocytes, Fstl1 increased glycerol release, cyclic GMP production, and hormone sensitive lipase activation, but these effects were attenuated by DIP2a knockdown. DIP2a gene expression in human adipose tissues correlated with serum glycerol concentrations during endurance exercise. CONCLUSIONS: Fstl1 is a myokine facilitating lipid mobilization during and after endurance exercise through DIP2a-mediated lipolytic effects in adipocytes.

Deficiency of Brummer lipase disturbs lipid mobilization and locomotion, and impairs reproduction due to defects in the eggshell ultrastructure in the insect vector Rhodnius prolixus.

Rhodnius prolixus is a hematophagous insect, which feeds on large and infrequent blood meals, and is a vector of trypanosomatids that cause Chagas disease. After feeding, lipids derived from blood meal are stored in the fat body as triacylglycerol, which is recruited under conditions of energy demand by lipolysis, where the first step is catalyzed by the Brummer lipase (Bmm), whose orthologue in mammals is the adipose triglyceride lipase (ATGL). Here, we investigated the roles of Bmm in adult Rhodnius prolixus under starvation, and after feeding. Its gene (RhoprBmm) was expressed in all the analyzed insect organs, and its transcript levels in the fat body were not altered by nutritional status. RNAi-mediated knockdown of RhoprBmm caused triacylglycerol retention in the fat body during starvation, resulting in larger lipid droplets and lower ATP levels compared to control females. The silenced females showed decreased flight capacity and locomotor activity. When RhoprBmm knockdown occurred before the blood meal and the insects were fed, the females laid fewer eggs, which collapsed and showed low hatching rates. Their hemolymph had reduced diacylglycerol content and vitellogenin concentration. The chorion (eggshell) of their eggs had no difference in hydrocarbon amounts or in dityrosine crosslinking levels compared to control eggs. However, it showed ultrastructural defects. These results demonstrated that Bmm activity is important not only to guarantee lipid mobilization to maintain energy homeostasis during starvation, but also for the production of viable eggs after a blood meal, by somehow contributing to the right formation of the egg chorion.

Coordinated Lipid Mobilization during Seed Development and Germination in Peanut (Arachis hypogaea L.).

Peanut (Arachis hypogaea L.) is one of the most important oil crops in the world due to its lipid-rich seeds. Lipid accumulation and degradation play crucial roles in peanut seed maturation and seedling establishment, respectively. Here, we utilized lipidomics and transcriptomics to comprehensively identify lipids and the associated functional genes that are important in the development and germination processes of a large-seed peanut variety. A total of 332 lipids were identified; triacylglycerols (TAGs) and diacylglycerols were the most abundant during seed maturation, constituting 70.43 and 16.11%, respectively, of the total lipids. Significant alterations in lipid profiles were observed throughout seed maturation and germination. Notably, TAG (18:1/18:1/18:2) and (18:1/18:2/18:2) peaked at 23386.63 and 23392.43 nmol/g, respectively, at the final stage of seed development. Levels of hydroxylated TAGs (HO-TAGs) increased significantly during the initial stage of germination. Accumulation patterns revealed an inverse relationship between free fatty acids and TAGs. Lipid degradation was determined to be regulated by diacylglycerol acyltransferase, triacylglycerol lipase, and associated transcription factors, predominantly yielding oleic acid, linoleic acid, and linolenic acid. Collectively, the results of this study provide valuable insights into lipid dynamics during the development and germination of large-seed peanuts, gene resources, and guiding future research into lipid accumulation in an economically important crop.

The ubiquitin-protein ligase MIEL1 localizes to peroxisomes to promote seedling oleosin degradation and lipid droplet mobilization.

Lipid droplets are organelles conserved across eukaryotes that store and release neutral lipids to regulate energy homeostasis. In oilseed plants, fats stored in seed lipid droplets provide fixed carbon for seedling growth before photosynthesis begins. As fatty acids released from lipid droplet triacylglycerol are catabolized in peroxisomes, lipid droplet coat proteins are ubiquitinated, extracted, and degraded. In Arabidopsis seeds, the predominant lipid droplet coat protein is OLEOSIN1 (OLE1). To identify genes modulating lipid droplet dynamics, we mutagenized a line expressing mNeonGreen-tagged OLE1 expressed from the OLE1 promoter and isolated mutants with delayed oleosin degradation. From this screen, we identified four miel1 mutant alleles. MIEL1 (MYB30-interacting E3 ligase 1) targets specific MYB transcription factors for degradation during hormone and pathogen responses [D. Marino et al., Nat. Commun. 4, 1476 (2013); H. G. Lee and P. J. Seo, Nat. Commun. 7, 12525 (2016)] but had not been implicated in lipid droplet dynamics. OLE1 transcript levels were unchanged in miel1 mutants, indicating that MIEL1 modulates oleosin levels posttranscriptionally. When overexpressed, fluorescently tagged MIEL1 reduced oleosin levels, causing very large lipid droplets. Unexpectedly, fluorescently tagged MIEL1 localized to peroxisomes. Our data suggest that MIEL1 ubiquitinates peroxisome-proximal seed oleosins, targeting them for degradation during seedling lipid mobilization. The human MIEL1 homolog (PIRH2; p53-induced protein with a RING-H2 domain) targets p53 and other proteins for degradation and promotes tumorigenesis [A. Daks et al., Cells 11, 1515 (2022)]. When expressed in Arabidopsis, human PIRH2 also localized to peroxisomes, hinting at a previously unexplored role for PIRH2 in lipid catabolism and peroxisome biology in mammals.

Cannabinoid-1 receptor activation modulates lipid mobilization and adipogenesis in the adipose tissue of dairy cows.

Amplified adipose tissue (AT) lipolysis and suppressed lipogenesis characterize the periparturient period of dairy cows. The intensity of lipolysis recedes with the progression of lactation; however, when lipolysis is excessive and prolonged, disease risk is exacerbated and productivity compromised. Interventions that minimize lipolysis while maintaining adequate supply of energy and enhancing lipogenesis may improve periparturient cows' health and lactation performance. Cannabinoid-1 receptor (CB1R) activation in rodent AT enhances the lipogenic and adipogenic capacity of adipocytes, yet the effects in dairy cow AT remain unknown. Using a synthetic CB1R agonist and an antagonist, we determined the effects of CB1R stimulation on lipolysis, lipogenesis, and adipogenesis in the AT of dairy cows. Adipose tissue explants were collected from healthy, nonlactating and nongestating (NLNG; n = 6) or periparturient (n = 12) cows at 1 wk before parturition and at 2 and 3 wk postpartum (PP1 and PP2, respectively). Explants were treated with the ß-adrenergic agonist isoproterenol (1 µM) in the presence of the CB1R agonist arachidonyl-2'-chloroethylamide (ACEA) ± the CB1R antagonist rimonabant (RIM). Lipolysis was quantified based on glycerol release. We found that ACEA reduced lipolysis in NLNG cows; however, it did not exhibit a direct effect on AT lipolysis in periparturient cows. Inhibition of CB1R with RIM in postpartum cow AT did not alter lipolysis. To evaluate adipogenesis and lipogenesis, preadipocytes isolated from NLNG cows' AT were induced to differentiate in the presence or absence of ACEA ± RIM for 4 and 12 d. Live cell imaging, lipid accumulation, and expressions of key adipogenic and lipogenic markers were assessed. Preadipocytes treated with ACEA had higher adipogenesis, whereas ACEA+RIM reduced it. Adipocytes treated with ACEA and RIM for 12 d exhibited enhanced lipogenesis compared with untreated cells (control). Lipid content was reduced in ACEA+RIM but not with RIM alone. Collectively, our results support that lipolysis may be reduced by CB1R stimulation in NLNG cows but not in periparturient cows. In addition, our findings demonstrate that adipogenesis and lipogenesis are enhanced by activation of CB1R in the AT of NLNG dairy cows. In summary, we provide initial evidence which supports that the sensitivity of the AT endocannabinoid system to endocannabinoids, and its ability to modulate AT lipolysis, adipogenesis, and lipogenesis, vary based on dairy cows' lactation stage.

FGF1 ameliorates obesity-associated hepatic steatosis by reversing IGFBP2 hypermethylation.

Obesity is a major contributing factor for metabolic-associated fatty liver disease (MAFLD). Fibroblast growth factor (FGF) 1 is the first paracrine FGF family member identified to exhibit promising metabolic regulatory properties capable of conferring glucose-lowering and insulin-sensitizing effect. This study explores the role and molecular underpinnings of FGF1 in obesity-associated hepatic steatosis. In a mouse high-fat diet (HFD)-induced MAFLD model, chronic treatment with recombinant FGF1(rFGF1) was found to effectively reduce the severity of insulin resistance, hyperlipidemia, and inflammation. FGF1 treatment decreased lipid accumulation in the mouse liver and palmitic acid-treated AML12 cells. These effects were associated with decreased mature form SREBF1 expression and its target genes FASN and SCD1. Interestingly, we uncovered that rFGF1 significantly induced IGFBP2 expression at both mRNA and protein levels in HFD-fed mouse livers and cultured hepatocytes treated with palmitic acid. Adeno-associated virus-mediated IGFBP2 suppression significantly diminished the therapeutic benefit of rFGF1 on MAFLD-associated phenotypes, indicating that IGFBP2 plays a crucial role in the FGF1-mediated reduction of hepatic steatosis. Further analysis revealed that rFGF1 treatment reduces the recruitment of DNA methyltransferase 3 alpha to the IGFBP2 genomic locus, leading to decreased IGFBP2 gene methylation and increased mRNA and protein expression. Collectively, our findings reveal FGF1 modulation of lipid metabolism via epigenetic regulation of IGFBP2 expression, and unravel the therapeutic potential of the FGF1-IGFBP2 axis in metabolic diseases associated with obesity.

Direct balancing of lipid mobilization and reactive oxygen species production by the epoxidation of fatty acid catalyzed by a cytochrome P450 protein during seed germination.

Fatty acid (FA) ß-oxidation provides energy for oil seed germination but also produces massive byproduct reactive oxygen species (ROS), posing potential oxidative damage to plant cells. How plants overcome the contradiction between energy supply and ROS production during seed germination remains unclear. In this study, we identified an Arabidopsis mvs1 (methylviologen-sensitive) mutant that was hypersensitive to ROS and caused by a missense mutation (G1349 substituted as A) of a cytochrome P450 gene, CYP77A4. CYP77A4 was highly expressed in germinating seedling cotyledons, and its protein is localized in the endoplasmic reticulum. As CYP77A4 catalyzes the epoxidation of unsaturated FA, disruption of CYP77A4 resulted in increased unsaturated FA abundance and over accumulated ROS in the mvs1 mutant. Consistently, scavenging excess ROS or blocking FA ß-oxidation could repress the ROS overaccumulation and hypersensitivity in the mvs1 mutant. Furthermore, H2 O2 transcriptionally upregulated CYP77A4 expression and post-translationally modified CYP77A4 by sulfenylating its Cysteine-456, which is necessary for CYP77A4's role in modulating FA abundance and ROS production. Together, our study illustrates that CYP77A4 mediates direct balancing of lipid mobilization and ROS production by the epoxidation of FA during seed germination.

Molecular identification and lipid mobilization role of adipokinetic hormone receptor in Spodoptera litura (F.).

Energy homeostasis is essential for organisms to maintain fluctuation in energy accumulation, mobilization. Lipids as the main energy reserve in insects, their metabolism is under the control of many physiological program. This study aimed to determine whether the adipokinetic hormone receptor (AKHR) was involved in the lipid mobilization in the Spodoptera litura. A full-length cDNA encoding AKHR was isolated from S. litura. The SlAKHR protein has a conserved seven-transmembrane domain which is the character of a putative G protein receptor. Expression profile investigation revealed that SlAKHR mRNA was highly expressed in immatural stage and abundant in fat body in newly emerged female adults. Knockdown of SlAKHR expression was achieved through RNAi by injecting double-stranded RNA (dsRNA) into the 6th instar larvae. The content of triacylgycerol (TAG) in the fat body increased significantly after the SlAKHR gene was knockdown. And decrease of TAG releasing to hemolymph with increase of free fatty acid (FFA) in hemolymph were observed when the SlAKHR gene was knowned-down. In addition, lipid droplets increased in fat body was also found. These results suggested that SlAKHR is critical for insects to regulate lipids metabolism.

Impacts of diethylhexyl phthalate and overfeeding on physical fitness and lipid mobilization in Danio rerio (zebrafish).

As the prevalence of obesity has steadily increased on a global scale, research has shifted to explore potential contributors to this pandemic beyond overeating and lack of exercise. Environmental chemical contaminants, known as obesogens, alter metabolic processes and exacerbate the obese phenotype. Diethylhexyl phthalate (DEHP) is a common chemical plasticizer found in medical supplies, food packaging, and polyvinyl materials, and has been identified as a probable obesogen. This study investigated the hypothesis that co-exposure to DEHP and overfeeding would result in decreased lipid mobilization and physical fitness in Danio rerio (zebrafish). Four treatment groups were randomly assigned: Regular Fed (control, 10 mg/fish/day with 0 mg/kg DEHP), Overfed (20 mg/fish/day with 0 mg/kg DEHP), Regular Fed + DEHP (10 mg/fish/day with 3 mg/kg DEHP), Overfed + DEHP (20 mg/fish/day with 3 mg/kg DEHP). After 24 weeks, swim tunnel assays were conducted on half of the zebrafish from each treatment to measure critical swimming speeds (Ucrit); the other fish were euthanized without swimming. Body mass index (BMI) was measured, and tissues were collected for blood lipid characterization and gene expression analyses. Co-exposure to DEHP and overfeeding decreased swim performance as measured by Ucrit. While no differences in blood lipids were observed with DEHP exposure, differential expression of genes related to lipid metabolism and utilization in the gastrointestinal and liver tissue suggests alterations in metabolism and lipid packaging, which may impact utilization and ability to mobilize lipid reserves during physical activity following chronic exposures.

The autophagy protein ATG9A enables lipid mobilization from lipid droplets.

The multispanning membrane protein ATG9A is a scramblase that flips phospholipids between the two membrane leaflets, thus contributing to the expansion of the phagophore membrane in the early stages of autophagy. Herein, we show that depletion of ATG9A does not only inhibit autophagy but also increases the size and/or number of lipid droplets in human cell lines and C. elegans. Moreover, ATG9A depletion blocks transfer of fatty acids from lipid droplets to mitochondria and, consequently, utilization of fatty acids in mitochondrial respiration. ATG9A localizes to vesicular-tubular clusters (VTCs) that are tightly associated with an ER subdomain enriched in another multispanning membrane scramblase, TMEM41B, and also in close proximity to phagophores, lipid droplets and mitochondria. These findings indicate that ATG9A plays a critical role in lipid mobilization from lipid droplets to autophagosomes and mitochondria, highlighting the importance of ATG9A in both autophagic and non-autophagic processes.

Lipolysis: cellular mechanisms for lipid mobilization from fat stores.

The perception that intracellular lipolysis is a straightforward process that releases fatty acids from fat stores in adipose tissue to generate energy has experienced major revisions over the last two decades. The discovery of new lipolytic enzymes and coregulators, the demonstration that lipophagy and lysosomal lipolysis contribute to the degradation of cellular lipid stores and the characterization of numerous factors and signalling pathways that regulate lipid hydrolysis on transcriptional and post-transcriptional levels have revolutionized our understanding of lipolysis. In this review, we focus on the mechanisms that facilitate intracellular fatty-acid mobilization, drawing on canonical and noncanonical enzymatic pathways. We summarize how intracellular lipolysis affects lipid-mediated signalling, metabolic regulation and energy homeostasis in multiple organs. Finally, we examine how these processes affect pathogenesis and how lipolysis may be targeted to potentially prevent or treat various diseases.

Early benefits of bariatric surgery on subclinical cardiac function: Contribution of visceral fat mobilization.

AIMS: We explored the early effects of bariatric surgery on subclinical myocardial function in individuals with severe obesity and preserved left ventricular (LV) ejection fraction. METHODS: Thirty-eight patients with severe obesity [body mass index (BMI) ≥35 kg/m2] and preserved LV ejection fraction (≥50%) who underwent bariatric surgery (biliopancreatic diversion with duodenal switch [BPD-DS]) (Surgery group), 19 patients with severe obesity managed with usual care (Medical group), and 18 age and sex-matched non-obese controls (non-obese group) were included. Left ventricular global longitudinal strain (LV GLS) was evaluated with echocardiography speckle tracking imaging. Abnormal myocardial function was defined as LV GLS <18%. RESULTS: Age of the participants was 42 ±â€¯11 years with a BMI of 48 ±â€¯8 kg/m2 (mean ±â€¯standard deviation); 82% were female. The percentage of total weight loss at 6 months after bariatric surgery was 26.3 ±â€¯5.2%. Proportions of hypertension (61 vs. 30%, P = 0.0005), dyslipidemia (42 vs. 5%, P = 0.0001) and type 2 diabetes (40 vs. 13%, P = 0.002) were reduced postoperatively. Before surgery, patients with obesity displayed abnormal subclinical myocardial function vs. non-obese controls (LV GLS, 16.3 ±â€¯2.5 vs. 19.6 ±â€¯1.7%, P < 0.001). Six months after bariatric surgery, the subclinical myocardial function was comparable to non-obese (LV GLS, 18.2 ±â€¯1.9 vs. 19.6 ±â€¯1.7%, surgery vs. non-obese, P = NS). On the contrary, half of individuals with obesity managed medically worsened their myocardial function during the follow-up (P = 0.002). Improvement in subclinical myocardial function following bariatric surgery was associated with changes in abdominal visceral fat (r = 0.43, P < 0.05) and inflammatory markers (r = 0.45, P < 0.01), whereas no significant association was found with weight loss or change in insulin sensitivity (HOMA-IR) (P > 0.05). In a multivariate model, losing visceral fat mass was independently associated with improved subclinical myocardial function. CONCLUSIONS: Bariatric surgery was associated with significant improvement in the metabolic profile and in subclinical myocardial function. Early improvement in subclinical myocardial function following bariatric surgery was related to a greater mobilization of visceral fat depot, linked to global fat dysfunction and cardiometabolic morbidity.

Embryonic exposure to low concentrations of aflatoxin B1 triggers global transcriptomic changes, defective yolk lipid mobilization, abnormal gastrointestinal tract development and inflammation in zebrafish.

Aflatoxin B1-contaminated feeds and foods induce various health problems in domesticated animals and humans, including tumor development and hepatotoxicity. Aflatoxin B1 also has embryotoxic effects in different livestock species and humans. However, it is difficult to distinguish between the indirect, maternally-mediated toxic effects and the direct embryotoxicity of aflatoxin B1 in mammals. In the present study, we investigated the aflatoxin B1-induced direct embryotoxic effects in a zebrafish embryo model system combining toxicological, transcriptomic, immunological, and biochemical approaches. Embryonic exposure to aflatoxin B1 induced significant changes at the transcriptome level resulting in elevated expression of inflammatory gene network and repression of lipid metabolism and gastrointestinal tract development-related gene sets. According to the gene expression changes, massive neutrophil granulocyte influx, elevated nitric oxide production, and yolk lipid accumulation were observed in the abdominal region of aflatoxin B1-exposed larvae. In parallel, aflatoxin B1-induced defective gastrointestinal tract development and reduced L-arginine level were found in our model system. Our results revealed the complex direct embryotoxic effects of aflatoxin B1, including inhibited lipid utilization, defective intestinal development, and inflammation.

GPR119 and GPR55 as Receptors for Fatty Acid Ethanolamides, Oleoylethanolamide and Palmitoylethanolamide.

Oleoylethanolamide and palmitoylethanolamide are members of the fatty acid ethanolamide family, also known as acylethanolamides. Their physiological effects, including glucose homeostasis, anti-inflammation, anti-anaphylactic, analgesia, and hypophagia, have been reported. They have affinity for different receptor proteins, including nuclear receptors such as PPARα, channels such as TRPV1, and membrane receptors such as GPR119 and GPR55. In the present review, the pathophysiological functions of fatty acid ethanolamides have been discussed from the perspective of receptor pharmacology and drug discovery.

Unravelling the Complex Interplay of Transcription Factors Orchestrating Seed Oil Content in Brassica napus L.

Transcription factors (TFs) and their complex interplay are essential for directing specific genetic programs, such as responses to environmental stresses, tissue development, or cell differentiation by regulating gene expression. Knowledge regarding TF-TF cooperations could be promising in gaining insight into the developmental switches between the cultivars of Brassica napus L., namely Zhongshuang11 (ZS11), a double-low accession with high-oil- content, and Zhongyou821 (ZY821), a double-high accession with low-oil-content. In this regard, we analysed a time series RNA-seq data set of seed tissue from both of the cultivars by mainly focusing on the monotonically expressed genes (MEGs). The consideration of the MEGs enables the capturing of multi-stage progression processes that are orchestrated by the cooperative TFs and, thus, facilitates the understanding of the molecular mechanisms determining seed oil content. Our findings show that TF families, such as NAC, MYB, DOF, GATA, and HD-ZIP are highly involved in the seed developmental process. Particularly, their preferential partner choices as well as changes in their gene expression profiles seem to be strongly associated with the differentiation of the oil content between the two cultivars. These findings are essential in enhancing our understanding of the genetic programs in both cultivars and developing novel hypotheses for further experimental studies.

Decellularized adipose tissue: A key factor in promoting fat regeneration by recruiting and inducing mesenchymal stem cells.

BACKGROUND: Decellularized adipose tissue (DAT) has attracted much attention due to its wide range of sources and adipose regeneration capacity. However, the lipogenic efficiency of DAT is still controversial due to its unclear mechanism. To this point, it is crucial to clarify the mechanism of DAT in promoting adipose regeneration Objective: This study aims to explore the mechanism of DAT promoting adipose regeneration and survival mechanism of DAT transplantation in vivo. METHODS: DAT preparation by repeated freeze-thaw, enzymatic digestion, and isopropanol degreasing. Histology, DAPI, immunohistochemistry, immunofluorescence and scanning electron microscopy confirmed the efficacy and reproducibility of these approaches. BM-MSCs, ADSCs and UCMSCs were cocultured with DAT for 14 days and then stained with oil red O. Adipogenic genes of three MSCs were detected by RT-PCR. DAT and adipose tissue were transplanted subcutaneously into the back of nude mice to observe medium and long-term morphological changes, vascularization, and lipid-forming efficiency. Mass spectrometry (MS)-based proteomic to analyze the adipogenic protein contents of DAT and adipose tissue. RESULTS: The DAT without any cellular components but with an abundance of collagen; neither DNA nor lipids were detected. Seeding experiments with MSCs indicated that the DAT provided an inductive microenvironment for adipogenesis, supporting the expression of the master regulators PPARγ. Within four months after transplantation, HE morphology of DAT was identical to adipose cells. Immunofluorescence markers CD31 and perilipin were increased in DAT, while the retention rate gradually decreased over time, eventually accounting for 33.7% of the original volume. MS-based proteomic analyses identified 1013 types of proteins in adipose tissue and 29 proteins in the DAT. Analyses of GO and KEGG databases suggested that DAT contained a variety of proteins involved in fat metabolism. CONCLUSIONS: DAT can interact with different types of MSCs and ultimately achieve adipose regeneration. The presence of multiple adipogenic proteins in DAT make it play a vital role in adipose regeneration. DAT is expected to be an ideal bio-derived scaffold for adipose tissue engineering.

Whole-body vibration promotes lipid mobilization in hypothalamic obesity rat.

OBJECTIVES: This study aimed to analyze the effect of whole-body vibration (WBV) on metabolic parameters using the monosodium l-glutamate (MSG) model of obesity. METHOD: MSG-obese rats that were exposed to WBV on a vibrating platform with 60 Hz frequency, 2 mm amplitude, three times/week, 10 min/day, during eight weeks (from postnatal day (PN) 80 to PN136). Blood glucose, creatine kinases (CK and CK-MB) and lipid profile through plasma and liver levels of lipids and lipoproteins were evaluated. Morphology and oxidative stress of adipose and hepatic tissues were further evaluated. RESULTS: When performing a WBV exercise, animals showed contrasting metabolic responses. Vibration Control group (CTL-WBV) presented a reduction in CK and liver triacylglycerol, an increase in glucose, lactate, total cholesterol, liver cholesterol, and LDL while MSG Vibration group (MSG-WBV) showed an increase in total triacylglycerol, VLDL, lactate, CK, liver cholesterol, additional liver lipid peroxidation and LDL, total cholesterol and CKMB reduction. CONCLUSION: Even although the MSG is a model of impacting injury, the metabolic demand of WBV exercise was able to induce mobilization of substrates, highlighting the lipid mobilization in obese animals, it should be used as a metabolic rehabilitation tool in patients with metabolic diseases, such as obesity and diabetes.