direct-cryosectioning-drosophila-heads-for-enhanced-brain

Direct Cryosectioning of <em>Drosophila</em> Heads for Enhanced Brain Fluorescence Staining and Immunostaining

Immunostaining Drosophila melanogaster brains is essential for exploring the mechanisms behind complex behaviors, neural circuits, and protein expression ...

novel-efficient-method-for-drosophila-heart-fluorescence-staining

Novel And Efficient Method for <em>Drosophila</em> Heart Fluorescence Staining with Cryosectioning

Drosophila heart models are widely employed in studying cardiac aging and modeling&#160;human cardiac diseases. However, the dissection of Drosophila ...

The University of Alabama at Birmingham

UAB Nathan Shock Center

Circadian rhythms are present throughout biology, from the molecular level to complex behaviors such as eating and sleeping. They are driven by molecular clocks within cells, and different tissues can have unique rhythms. Circadian disruption can trigger obesity and other common metabolic disorders such as aging, diabetes, and cardiovascular disease, and circadian genes control metabolism. At an organismal level, feeding and fasting rhythms are key drivers of circadian rhythms. This underscores the bidirectional relationship between metabolism and circadian rhythms, and many metabolic disorders have circadian disruption or misalignment. Therefore, studying circadian rhythms may offer new avenues for understanding the etiology and management of obesity. This review describes how circadian rhythm dysregulation is linked with cardiometabolic disorders and how the lifestyle intervention of time-restricted feeding (TRF) regulates them. TRF reinforces feeding-fasting rhythms without reducing caloric intake and ameliorates metabolic disorders such as obesity and associated cardiac dysfunction, along with reducing inflammation. TRF optimizes the expression of genes and pathways related to normal metabolic function, linking metabolism with TRF's benefits and demonstrating the molecular link between metabolic disorders and circadian rhythms. Thus, TRF has tremendous therapeutic potential that could be easily adopted to reduce obesity-linked dysfunction and cardiometabolic disorders.

Circadian-mediated regulation of cardiometabolic disorders and aging with time-restricted feeding.

Obesity caused by genetic and environmental factors can lead to compromised skeletal muscle function. Time-restricted feeding (TRF) has been shown to prevent muscle function decline from obesogenic challenges; however, its mechanism remains unclear. Here we demonstrate that TRF upregulates genes involved in glycine production (Sardh and CG5955) and utilization (Gnmt), while Dgat2, involved in triglyceride synthesis is downregulated in Drosophila models of diet- and genetic-induced obesity. Muscle-specific knockdown of Gnmt, Sardh, and CG5955 lead to muscle dysfunction, ectopic lipid accumulation, and loss of TRF-mediated benefits, while knockdown of Dgat2 retains muscle function during aging and reduces ectopic lipid accumulation. Further analyses demonstrate that TRF upregulates the purine cycle in a diet-induced obesity model and AMPK signaling-associated pathways in a genetic-induced obesity model. Overall, our data suggest that TRF improves muscle function through modulations of common and distinct pathways under different obesogenic challenges and provides potential targets for obesity treatments.

Time-restricted feeding promotes muscle function through purine cycle and AMPK signaling in Drosophila obesity models.

The Drosophila model is pivotal in deciphering the pathophysiological underpinnings of various human ailments, notably aging and cardiovascular diseases. Cutting-edge imaging techniques and physiology yield vast high-resolution videos, demanding advanced analysis methods. Our platform leverages deep learning to segment optical microscopy images of Drosophila hearts, enabling the quantification of cardiac parameters in aging and dilated cardiomyopathy (DCM). Validation using experimental datasets confirms the efficacy of our aging model. We employ two innovative approaches deep-learning video classification and machine-learning based on cardiac parameters to predict fly aging, achieving accuracies of 83.3% (AUC 0.90) and 79.1%, (AUC 0.87) respectively. Moreover, we extend our deep-learning methodology to assess cardiac dysfunction associated with the knock-down of oxoglutarate dehydrogenase (OGDH), revealing its potential in studying DCM. This versatile approach promises accelerated cardiac assays for modeling various human diseases in Drosophila and holds promise for application in animal and human cardiac physiology under diverse conditions.

Automated assessment of cardiac dynamics in aging and dilated cardiomyopathy Drosophila models using machine learning.

This review explores the complex interplay between genetic predispositions to obesity, circadian rhythms, metabolic regulation, and sleep. It highlights how genetic factors underlying obesity exacerbate metabolic dysfunction through circadian misalignment and examines promising interventions to mitigate these effects.

ArticleTotal : 2	Year
Publication title Cited by 3	2025
Publication title	2025

Article	Year
Circadian-mediated regulation of cardiometabolic disorders and aging with time-restricted feeding. Obesity (Silver Spring, Md.)\| PubMed ID: 36623845	2023
Time-restricted feeding promotes muscle function through purine cycle and AMPK signaling in Drosophila obesity models. Nature communications\| PubMed ID: 36810287	2023
Automated assessment of cardiac dynamics in aging and dilated cardiomyopathy Drosophila models using machine learning. Communications biology\| PubMed ID: 38849449	2024
The Interplay of Genetic Predisposition, Circadian Misalignment, and Metabolic Regulation in Obesity. Current obesity reports\| PubMed ID: 40024983	2025

Girish C. Melkani

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