scholarly journals Obesity-associated cardiac dysfunction in starvation-selected Drosophila melanogaster

2015 ◽  
Vol 309 (6) ◽  
pp. R658-R667 ◽  
Author(s):  
Christopher M. Hardy ◽  
Ryan T. Birse ◽  
Matthew J. Wolf ◽  
Lin Yu ◽  
Rolf Bodmer ◽  
...  

There is a clear link between obesity and cardiovascular disease, but the complexity of this interaction in mammals makes it difficult to study. Among the animal models used to investigate obesity-associated diseases, Drosophila melanogaster has emerged as an important platform of discovery. In the laboratory, Drosophila can be made obese through lipogenic diets, genetic manipulations, and adaptation to evolutionary stress. While dietary and genetic changes that cause obesity in flies have been demonstrated to induce heart dysfunction, there have been no reports investigating how obesity affects the heart in laboratory-evolved populations. Here, we studied replicated populations of Drosophila that had been selected for starvation resistance for over 65 generations. These populations evolved characteristics that closely resemble hallmarks of metabolic syndrome in mammals. We demonstrate that starvation-selected Drosophila have dilated hearts with impaired contractility. This phenotype appears to be correlated with large fat deposits along the dorsal cuticle, which alter the anatomical position of the heart. We demonstrate a strong relationship between fat storage and heart dysfunction, as dilation and reduced contractility can be rescued through prolonged fasting. Unlike other Drosophila obesity models, the starvation-selected lines do not exhibit excessive intracellular lipid deposition within the myocardium and rather store excess triglycerides in large lipid droplets within the fat body. Our findings provide a new model to investigate obesity-associated heart dysfunction.

2021 ◽  
Vol 3 (3) ◽  
pp. 429-441
Author(s):  
Ilya A. Solovev ◽  
Mikhail V. Shaposhnikov ◽  
Alexey A. Moskalev

Chronobiotics are a group of drugs, which are utilized to modify circadian rhythms targeting clock-associated molecular mechanisms. The circadian clock is known as a controller of numerous processes in connection with aging. Hypothesis: KL001 and KS15 targeting CRY, affect lifespan, locomotor activity and circadian rhythm of Drosophila melanogaster. We observed a slight (2%, p < 0.001) geroprotective effect on median lifespan (5 µM solution of KL001 in 0.1% DMSO) and a 14% increase in maximum lifespan in the same group. KS15 10 µM solution extended males’ median lifespan by 8% (p < 0.05). The statistically significant positive effects of KL001 and KS15 on lifespan were not observed in female flies. KL001 5 µM solution improved locomotor activity in young male imagoes (p < 0.05), elevated morning activity peak in aged imagoes and modified robustness of their circadian rhythms, leaving the period intact. KS15 10 µM solution decreased the locomotor activity in constant darkness and minimized the number of rhythmic flies. KL001 5 µM solution improved by 9% the mean starvation resistance in male flies (p < 0.01), while median resistance was elevated by 50% (p < 0.0001). This phenomenon may suggest the presence of the mechanism associated with improvement of fat body glucose depos’ utilization in starvation conditions which is activated by dCRY binding KL001.


Author(s):  
Ilya Solovev ◽  
Mikhail Shaposhnikov ◽  
Alexey Moskalev

Chronobiotics is a group of drugs utilized to modify circadian rhythms targeting clock-associated molecular mechanisms. The circadian clock is known as a controller of numerous processes standing behind aging. Hypothesis: KL001 and KS15 targeting CRY, affect lifespan, locomotor activity and circadian rhythm of Drosophila melanogaster. We observed a slight (2%, p&lt;0.001) geroprotective effect on median lifespan (5 &micro;M solution of KL001 in 0.1% DMSO) and a 14% increase in maximum lifespan in the same group. KS15 10 &micro;M solution extended males&rsquo; median lifespan by 8% (p &lt;0.05). The statistically significant positive effects of KL001 and KS15 on lifespan were not observed in female flies. KL001 5 &micro;M solution improved locomotor activity in young male imagos (p&lt;0.05) and elevated morning activity peak in aged imagos and modified robustness of circadian rhythms, leaving the period intact. KS15 10 &micro;M solution decreased the locomotor activity in constant darkness and minimized the number of rhythmic flies. KL001 5 &micro;M solution improved by 9% the mean starvation resistance in male flies (p&lt;0.01), while median resistance was elevated by 50% (p&lt;0.0001). This phenomenon may suggest the presence of the mechanism associated with improvement of fat body glucose depos&rsquo; utilization in starvation conditions which is activated by dCRY binding KL001.


2001 ◽  
Vol 42 (2) ◽  
pp. 225-234 ◽  
Author(s):  
Estela L. Arrese ◽  
Justin L. Gazard ◽  
Matthew T. Flowers ◽  
Jose L. Soulages ◽  
Michael A. Wells

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Ryotaro Maeda ◽  
Daisuke Kami ◽  
Akira Shikuma ◽  
Yosuke Suzuki ◽  
Toshihiko Taya ◽  
...  

AbstractThe RNA decay pathway plays key regulatory roles in cell identities and differentiation processes. Although adipogenesis is transcriptionally and epigenetically regulated and has been thoroughly investigated, how RNA metabolism that contributes to the stability of phenotype-shaping transcriptomes participates in differentiation remains elusive. In this study, we investigated Ddx6, an essential component of processing bodies (PBs) that executes RNA decay and translational repression in the cytoplasm and participates in the cellular transition of reprogramming. Upon adipogenic induction, Ddx6 dynamically accumulated to form PBs with a binding partner, 4E-T, at the early phase prior to emergence of intracellular lipid droplets. In contrast, preadipocytes with Ddx6 knockout (KO) or 4E-T knockdown (KD) failed to generate PBs, resulting in significant suppression of adipogenesis. Transcription factors related to preadipocytes and negative regulators of adipogenesis that were not expressed under adipogenic stimulation were maintained in Ddx6-KO and 4E-T-KD preadipocytes under adipogenic induction. Elimination of Dlk1, a major negative regulator of adipogenesis, in 3T3L1 Ddx6-KO cells did not restore adipogenic differentiation capacity to any extent. Similar to murine cells, human primary mesenchymal stem cells, which can differentiate into adipocytes upon stimulation with adipogenic cocktails, required DDX6 to maturate into adipocytes. Therefore, RNA decay of the entire parental transcriptome, rather than removal of a strong negative regulator, could be indispensable for adipogenesis.


iScience ◽  
2021 ◽  
Vol 24 (4) ◽  
pp. 102288
Author(s):  
Annelie Blumrich ◽  
Georg Vogler ◽  
Sandra Dresen ◽  
Soda Balla Diop ◽  
Carsten Jaeger ◽  
...  

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 769
Author(s):  
Yuko Hara ◽  
Kenichi Goda ◽  
Shinichi Hirooka ◽  
Takehiro Mitsuishi ◽  
Masahiro Ikegami ◽  
...  

We previously reported that superficial non-ampullary duodenal tumors (SNADETs) commonly had a whitish mucosal surface, named milk-white mucosa (MWM). The aim of this study was to evaluate the association of MWM with epithelial intracellular lipid droplets (immunohistochemically stained by adipose differentiation-related protein (ADRP)) and histological tumor grades. We reviewed endoscopic images and the histopathology of SNADETs resected en bloc endoscopically. We analyzed the correlation between the positive rates of endoscopic MWM in preoperative endoscopy and resected specimens, and ADRP-positive rates in the resected specimens. Associations between the MWM-positive rates and tumor grades, high-grade intraepithelial neoplasia (HGIN)/intramucosal carcinoma (IC), and low-grade intraepithelial neoplasia (LGIN) were analyzed. All the 92 SNADETs analyzed were <20 mm and histologically classified into 39 HGIN/IC and 53 LGIN. Spearman’s rank correlation coefficient showed a significant correlation between MWM-positive and ADRP-positive rates (p < 0.001). MWM-positive rates were significantly lower in the HGIN/IC than in the LGIN in preoperative endoscopy (p < 0.001) and resected specimens (p = 0.02). Our results suggest that endoscopic MWM is closely associated with epithelial intracellular lipid droplets and that the MWM-positive rate may be a predictor of histological grade in small SNADETs.


2017 ◽  
Vol 28 (5) ◽  
pp. 1363-1370 ◽  
Author(s):  
Hanna Appelqvist ◽  
Kati Stranius ◽  
Karl Börjesson ◽  
K. Peter. R. Nilsson ◽  
Christine Dyrager

2020 ◽  
Author(s):  
Ravinder Kumar ◽  
Muhammad Arifur Rahman ◽  
Taras Y. Nazarko

AbstractIn yeast, the selective autophagy of intracellular lipid droplets (LDs) or lipophagy can be induced by either nitrogen (N) starvation or carbon limitation (e.g. in the stationary (S) phase). We developed the yeast, Komagataella phaffii (formerly Pichia pastoris), as a new lipophagy model and compared the N-starvation and S-phase lipophagy in over 30 autophagy-related mutants using the Erg6-GFP processing assay. Surprisingly, two lipophagy pathways had hardly overlapping stringent molecular requirements. While the N-starvation lipophagy strictly depended on the core autophagic machinery (Atg1-Atg9, Atg18 and Vps15), vacuole fusion machinery (Vam7 and Ypt7) and vacuolar proteolysis (proteinases A and B), only Atg6 and proteinases A and B were essential for the S-phase lipophagy. The rest of the proteins were only partially required in the S-phase. Moreover, we isolated the prl1 (for positive regulator of lipophagy 1) mutant affected in the S-phase lipophagy but not N-starvation lipophagy. The prl1 defect was at a stage of delivery of the LDs from the cytoplasm to the vacuole further supporting mechanistically different nature of the two lipophagy pathways. Taken together, our results suggest that N-starvation and S-phase lipophagy have distinct molecular mechanisms.


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