scholarly journals Neurosecretory protein GL-induced fat accumulation is accompanied by repressing the immune-inflammatory response in the adipose tissue of mice

2021 ◽  
Author(s):  
Keisuke Fukumura ◽  
Yuki Narimatsu ◽  
Eiko Iwakoshi-Ukena ◽  
Megumi Furumitsu ◽  
Hidemasa Bono ◽  
...  

AbstractWe have recently identified neurosecretory protein GL (NPGL), a small secretory protein expressed in the vertebrate hypothalamus, as an orexigenic factor with remarkable fat accumulation by overexpression of the NPGL precursor gene (Npgl) for two months. In the present study, we analyzed the effects of short-term Npgl overexpression for 18 days as the early stage of obesity to address the mechanisms underlying obese-like phenotype. Similar to previous studies, short-term Npgl overexpression stimulated food intake and fat accumulation in the white adipose tissues (WAT), whereas the masses of the brown adipose tissue, testis, liver, heart, and muscle remained unchanged. In addition, we observed increased blood insulin and leptin levels due to Npgl overexpression, while little changes were induced in blood glucose, free fatty acids, triglyceride, and cholesterol levels. Furthermore, transcriptome analysis of the inguinal WAT using RNA-sequencing technique revealed that overexpression of Npgl upregulated the genes involved in cytoskeleton regulation, whereas it decreased those involved in immune-inflammatory responses. These results suggest that NPGL plays a crucial role in enlarging adipocytes and suppressing inflammation to avoid metabolic abnormalities, eventually contributing to accelerating energy storage.

2020 ◽  
Vol 21 (22) ◽  
pp. 8606
Author(s):  
Shogo Moriwaki ◽  
Yuki Narimatsu ◽  
Keisuke Fukumura ◽  
Eiko Iwakoshi-Ukena ◽  
Megumi Furumitsu ◽  
...  

RFamide-related peptide-3 (RFRP-3), the mammalian ortholog of avian gonadotropin-inhibitory hormone (GnIH), plays a crucial role in reproduction. In the present study, we explored the other functions of RFRP-3 by investigating the effects of chronic intracerebroventricular infusion of RFRP-3 (6 nmol/day) for 13 days on energy homeostasis in lean male C57BL/6J mice. The infusion of RFRP-3 increased cumulative food intake and body mass. In addition, the masses of brown adipose tissue (BAT) and the liver were increased by the administration of RFRP-3, although the mass of white adipose tissue was unchanged. On the other hand, RFRP-3 decreased O2 consumption, CO2 production, energy expenditure, and core body temperature during a short time period in the dark phase. These results suggest that the increase in food intake and the decrease in energy expenditure contributed to the gain of body mass, including the masses of BAT and the liver. The present study shows that RFRP-3 regulates not only reproductive function, but also energy metabolism, in mice.


2020 ◽  
Vol 13 (8) ◽  
pp. 76
Author(s):  
C. E. Abra ◽  
J. R. Assis

Obesity is a result of energy imbalance caused by excess caloric intake in relation to energy demand. Metabolic functions and fat behavior led to the classification of adipose tissue deposits into three types, white, brown and beige. White adipose tissue (BAT) and brown adipose tissue (WAT) have distinct functions, expending fat on heat production and storing fat as an energy source, respectively. However, brown adipocytes can appear in WAT by a process called WAT darkening, forming the beige adipose tissue. Research suggests that polyphenols play a vital role in preventing and managing obesity and its comorbidities. In this context, we aimed to perform a literature review on the use of the main antiobesity polyphenols as well as the mechanisms by which they perform effects. The main antiobesity polyphenols are catechins, resveratrol, quercetin, berberine, curcumin, thymol, chrysin, magnolol, honokiol, capsaicin and capsainoids. And the mechanisms of its effects are linked to gene transcription (PGC-1α, PRDM16 and UPC1) for the modification of WAT in beige adipose tissue that resembles morphophysiological with BAT, favoring fat burning by β-oxidation of fatty acids, translating into potential use for reduction and prevention of body fat accumulation. Therefore, the action of these polyphenols for the loss and reduction in body fat accumulation is strongly evidenced. Future studies should be directed to the use of polyphenols in humans, so that they can stipulate adequate doses for antiobesity use.


Author(s):  
Nela Maksimovic ◽  
Vanja Vidovic ◽  
Tatjana Damnjanovic ◽  
Biljana Jekic ◽  
Nada Majkic Singh ◽  
...  

IntroductionPositive regulatory domain containing 16 (PRDM16) protein represents the key regulator of brown adipose tissue (BAT) development. It induces brown fat phenotype and represses white adipose tissue specific genes through the association with C-terminal binding co-repressor proteins (CtBP1 and CtBP2). In healthy adults presence of BAT has been associated with lower glucose, total cholesterol and LDL (low-density lipoprotein) cholesterol levels. Our aim was to analyze the association of PRDM16 gene (rs12409277) and CtBP2 gene (rs1561589) polymorphisms with body mass index (BMI), fasting glucose level and lipid profile of adolescents.Material and methodsOur study included 295 healthy school children, 145 boys (49.2%) and 150 girls (50.8%), 15 years of age. Genotypes for the selected polymorphisms were detected by the real-time PCR method. Age, gender, height, weight, lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and fasting glucose levels were recorded.ResultsWe did not find a statistically significant association of rs12409277 and rs1561589 polymorphisms with BMI, fasting glucose and lipid profile of adolescents. We further analyzed the combined effect of the two SNPs and the statistical analysis showed that carriers of CT genotype of rs12409277 polymorphism and GG genotype of rs1561589 polymorphism had significantly lower total cholesterol (p = 0.001) and LDL cholesterol (p = 0.008) levels compared to all other groups of genotypes.ConclusionsOur study suggests that rs12409277 and rs1561589 polymorphism might have an influence on total and LDL cholesterol levels in adolescents. Larger studies should be performed in order to confirm our results.


Author(s):  
Peter Aldiss ◽  
Jo Lewis ◽  
David Boocock ◽  
Amanda Miles ◽  
Ian Bloor ◽  
...  

Brown adipose tissue (BAT) function may depend on its anatomical location and developmental origin. Interscapular BAT (iBAT) regulates acute macronutrient metabolism, whilst perivascular BAT (PVAT) regulates vascular function. Although phenotypically similar, whether these depots respond differently to acute nutrient excess is unclear. Given their distinct anatomical locations and developmental origins and we hypothesised that iBAT and PVAT would respond differently to brief period of nutrient excess. Sprague-Dawley rats aged 12 weeks (n = 12) were fed either a standard (10% fat, n = 6) or high fat diet (HFD: 45% fat, n = 6) for 72 h and housed at thermoneutrality. Following an assessment of whole body physiology, fat was collected from both depots for analysis of gene expression and the proteome. HFD consumption for 72 h induced rapid weight gain (c. 2.6%) and reduced serum NEFA with no change in either total adipose or depot mass. In iBAT, an upregulation of genes involved in insulin signalling and lipid metabolism was accompanied by enrichment of lipid-related processes and functions, plus glucagon and PPAR signalling pathways. In PVAT, HFD induced a pronounced down-regulation of multiple metabolic pathways which was accompanied with increased abundance of proteins involved in apoptosis (e.g. Hdgf and Ywaq) and toll-like receptor signalling (Ube2n). There was also an enrichment of DNA-related processes and functions (e.g., nucleosome assembly and histone exchange) and RNA degradation and cell adhesion pathways. In conclusion, we show that iBAT and PVAT elicit divergent responses to short-term nutrient excess highlighting early adaptations in these depots before changes in fat mass.


2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Nicholas Wawrzyniak ◽  
Andrew Duarte ◽  
Linda Nguyen ◽  
Anna‐Maria Joseph ◽  
Andrew Layne ◽  
...  

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1065 ◽  
Author(s):  
Peter Aldiss ◽  
Jo E. Lewis ◽  
David J. Boocock ◽  
Amanda K. Miles ◽  
Ian Bloor ◽  
...  

Brown adipose tissue (BAT) function may depend on its anatomical location and developmental origin. Interscapular BAT (iBAT) regulates acute macronutrient metabolism, whilst perivascular BAT (PVAT) regulates vascular function. Although phenotypically similar, whether these depots respond differently to acute nutrient excess is unclear. Given their distinct anatomical locations and developmental origins and we hypothesised that iBAT and PVAT would respond differently to brief period of nutrient excess. Sprague-Dawley rats aged 12 weeks (n=12) were fed either a standard (10% fat, n=6) or high fat diet (HFD: 45% fat, n=6) for 72h and housed at thermoneutrality. Following an assessment of whole body physiology, fat was collected from both depots for analysis of gene expression and the proteome. HFD consumption for 72h induced rapid weight gain (c. 2.6%) and reduced serum non-esterified fatty acids (NEFA) with no change in either total adipose or depot mass. In iBAT, an upregulation of genes involved in insulin signalling and lipid metabolism was accompanied by enrichment of lipid-related processes and functions, plus glucagon and peroxisome proliferator-activated receptor (PPAR) signalling pathways. In PVAT, HFD induced a pronounced down-regulation of multiple metabolic pathways which was accompanied with increased abundance of proteins involved in apoptosis (e.g., Hdgf and Ywaq) and toll-like receptor signalling (Ube2n). There was also an enrichment of DNA-related processes and functions (e.g., nucleosome assembly and histone exchange) and RNA degradation and cell adhesion pathways. In conclusion, we show that iBAT and PVAT elicit divergent responses to short-term nutrient excess highlighting early adaptations in these depots before changes in fat mass.


2020 ◽  
Author(s):  
Susie S.Y. Huang ◽  
Melanie Makhlouf ◽  
Eman H. AbouMoussa ◽  
Mayra L. Ruiz Tejada Segura ◽  
Lisa S. Mathew ◽  
...  

ABSTRACTDifferent fasting regimens are known to promote health, mitigate chronic immunological disorders, and improve age-related pathophysiological parameters in animals and humans. Indeed, several clinical trials are currently ongoing using fasting as a potential therapy for a wide range of conditions. Fasting alters metabolism by acting as a reset for energy homeostasis. However, the molecular mechanisms underlying the beneficial effects of short-term fasting (STF) are still not well understood, particularly at the systems or multi-organ level. Here, we investigated the dynamic gene expression patterns associated with six periods of STF in nine different mouse organs. We cataloged the transcriptional dynamics within and between organs during STF and discovered differential temporal effects of STF among organs. Using gene ontology enrichment analysis, we identified an organ network sharing 37 common biological pathways perturbed by STF. This network incorporates the brain, liver, interscapular brown adipose tissue, and posterior-subcutaneous white adipose tissue, hence we named it the brain-liver-fats organ network. Using Reactome pathways analysis, we identified the immune system, dominated by T cell regulation processes, as a central and prominent target of systemic modulations during STF in this organ network. The changes we identified in specific immune components point to the priming of adaptive immunity and parallel the fine-tuning of innate immune signaling. Our study provides a comprehensive multi-organ transcriptomic profiling of mice subjected to multiple periods of STF, and adds new insights into the molecular modulators involved in the systemic immuno-transcriptomic changes that occur during short-term energy loss.


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