Obese fruit flies are the test subjects in a nature communication Studying the causes of muscle function decline due to obesity. In humans, skeletal muscle plays a crucial role in metabolism, and muscle dysfunction due to human obesity can lead to insulin resistance and reduced energy levels.
Interestingly, studies in various animal models have shown that time-restricted feeding – a natural non-pharmaceutical intervention – protects against obesity, aging and circadian disorders in peripheral tissues such as skeletal muscle. However, the mechanisms underlying these benefits were not known.
In fruit flies—scientifically known as Drosophila melanogaster—obese Drosophila exposed to adipogenic challenges and treated with time-restricted feeding showed improved muscle performance, reduced intramuscular fat, lower phospho-AKT levels, and a reduction in the insulin resistance marker. Intramyocellular lipids and triglycerides, which are deposited in skeletal muscle cells, can be harmful if not routinely broken down.
The current study, led by researcher Girish Melkani, Ph.D. from the University of Alabama at Birmingham, provides a potential mechanistic basis for the benefits conferred by time-restricted feeding. Melkani and colleagues found that time-restricted feeding induced upregulation of genes related to glycine production and utilization and down-regulation of a key enzyme involved in triglyceride synthesis under all time-restricted feeding conditions.
In addition, time-limited feeding induced upregulation of genes and increase in metabolites related to purine cycle in the high-fat fruit fly model of obesity, and it led to upregulation of genes and increase in metabolites related to glycolysis, glycogen metabolism, etc. tricarboxylic acid cycle and the electron transport chain linked by AMP kinase signaling in a fruit fly genetic model of obesity mutated to sphingosine kinase or Sk2.
“The prevalence of obesity continues to be a growing problem worldwide, linked to crippling health care and economic burdens,” said Melkani, associate professor in the Division of Molecular and Cellular Pathology at UAB’s Department of Pathology. “Obesity is associated with various comorbidities, particularly high-calorie diets and genetic predisposition. This study sheds light on possible mechanisms behind the protective properties of a time-restricted diet against skeletal muscle dysfunction and metabolic impairment caused by obesity.”
The results could pave the way for future time-limited nutritional studies in muscle and offer a natural and affordable form of alternative therapy to treat pathologies related to metabolism and obesity, Melkani says.
Melkani also described his long-term research goals. “Recent genome-wide association studies and exon sequencing approaches have identified an association of additional genes with genetic obesity. Obesity is strongly linked to cardiovascular disease and dementia. However, the mechanistic linkage remains poorly understood, and urgent interventions are needed to alleviate these disruptions.
“Our mechanistic approach — along with interventions including time-restricted eating — will be very useful to address and treat the disparities in obesity, cardiovascular disease and dementia observed in the Deep South.”
The fruit fly is an accessible model for studying human metabolic diseases. In the current study, the high-fat diet fruit fly model of obesity has a diet supplemented with 5 percent coconut oil, and the fruit flies are allowed to eat 24 hours a day. The time-restricted feeding, high-fat diet Fruit flies only have access to the high-fat diet for 12 hours a day. The Sk2 fly model of obesity has a mutation in the Sk2 gene that results in a characteristic accumulation of ceramide, which is implicated as a factor in obesity.
Experimental methods for muscle performance in the current study included flight tests in which 10 to 20 fruit flies were released into a Plexiglas box and each fly’s ability to fly up, horizontally, down or not at all was measured. Methods also included cytological analysis of muscle tissue and abdominal fat bodies, gene expression analysis, and measurement of glycine, ATP, and metabolite levels.
Christopher Livelo et al, Time-restricted feeding promotes muscle function through the purine cycle and AMPK signaling in Drosophila obesity models, nature communication (2023). DOI: 10.1038/s41467-023-36474-4
Provided by the University of Alabama at Birmingham
Citation: Rhythmic Eating Pattern Preserves Muscle Function in Fruit Flies Under Obesity (2023 March 4) Retrieved March 4, 2023 from https://phys.org/news/2023-03-rhythmic-pattern-fruit-fly-muscle.html
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