The fat–muscle communication regulates metabolism and involves circulating signals like adiponectin. Modulation of this cross-talk could benefit muscle bioenergetics and exercise tolerance in conditions like obesity. Chronic daily intake of exogenous glucocorticoids produces or exacerbates metabolic stress, often leading to obesity. In stark contrast to the daily intake, we discovered that intermittent pulses of glucocorticoids improve dystrophic muscle metabolism. However, the underlying mechanisms, particularly in the context of obesity, are still largely unknown. Here we report that in mice with diet-induced obesity, intermittent once-weekly prednisone increased total and high-molecular weight adiponectin levels and improved exercise tolerance and energy expenditure. These effects were dependent upon adiponectin, as shown by genetic ablation of the adipokine. Upregulation of Adipoq occurred through the glucocorticoid receptor (GR), as this effect was blocked by inducible GR ablation in adipocytes. The treatment increased the muscle metabolic response of adiponectin through the CAMKK2–AMPK cascade. Our study demonstrates that intermittent glucocorticoids produce healthful metabolic remodeling in diet-induced obesity.
Objective: Autonomic dysfunction qualifies a major public health problems owing to their high prevalence and incidence globally. Among many predisposing factor of autonomic neuropathy such as age, gender, genetic, diabetes etc, obesity also has significant . impact Although a lot of progress has been achieved in past decade on accessibility and awareness about health, the obesity remains impending and burgeoning health concern in Nepal. With this trend, we can foresee that the Body Mass Index (BMI) one of the commonly used indirect measure of obesity, might potentially turn out to be one of the leading factor of autonomic dysfunction.
Methods: 100 healthy subjects were screened and divided into 2 groups- Group I (BMI>30) and Group II (BMI< 30). Height & weight were measured & BMI was calculated. Resting heart rate (RHR) was recorded with Lead II of ECG. Blood pressure (BP) and Heart Rate (HR) were recorded in supine position and on immediate standing. Cold pressure test (CPT): Resting BP was recorded in sitting position. Then the subjects were asked to immerse the hand in cold water, and the BP was measured from other hand. Data was analyzed using SPSS 16 (Statistical Package for Social Science).
Result: Our result showed that RHR of Group I (79.32±4.22) was higher than that of Group II (74.38±7.26). However, on student –T test, BP and HR response to immediate standing (P=0.34 &P=0.23 respectively) were non-significant between group I and group II person. When the correlation was done for the change in BP in response to CPT in between obese and non-obese person it was found to be significant (P=0.04).
Conclusion: Our data suggests that the BMI can be a predictor of autonomic dysfunction.
The development of a complex organ involves the specification and differentiation of diverse cell types constituting that organ. Two major cell subtypes, contractile cardial cells (CCs) and nephrocytic pericardial cells (PCs), comprise the
Drosophila
heart. Binding sites for Suppressor of Hairless [Su(H)], an integral transcription factor in the Notch signaling pathway, are enriched in the enhancers of PC-specific genes. Here we show three distinct mechanisms regulating the expression of two different PC-specific genes,
Holes in muscle
(
Him
), and
Zn finger homeodomain 1
(
zfh1
).
Him
transcription is activated in PCs in a permissive manner by Notch signaling: in the absence of Notch signaling, Su(H) forms a repressor complex with co-repressors and binds to the
Him
enhancer, repressing its transcription; upon alleviation of this repression by Notch signaling,
Him
transcription is activated. In contrast,
zfh1
is transcribed by a Notch-instructive mechanism in most PCs, where mere alleviation of repression by preventing the binding of Su(H)-co-repressor complex is not sufficient to activate transcription. Our results suggest that upon activation of Notch signaling, the Notch intracellular domain associates with Su(H) to form an activator complex that binds to the
zfh1
enhancer, and that this activator complex is necessary for bringing about
zfh1
transcription in these PCs. Finally, a third, Notch-independent mechanism activates
zfh1
transcription in the remaining,
even skipped
-expressing, PCs. Collectively, our data show how the same feature, enrichment of Su(H) binding sites in PC-specific gene enhancers, is utilized by two very distinct mechanisms, one permissive, the other instructive, to contribute to the same overall goal: the specification and differentiation of a cardiac cell subtype by activation of the pericardial gene program. Furthermore, our results demonstrate that the
zfh1
enhancer drives expression in two different domains using distinct Notch-instructive and Notch-independent mechanisms.
Skeletal muscle disorders commonly affect the function and integrity of muscles. Novel interventions bring new potential to rescue or alleviate the symptoms associated with these disorders. In vivo and in vitro testing in mouse models allows quantitative evaluation of the degree of muscle dysfunction, and therefore, the level of potential rescue/restoration by the target intervention. Several resources and methods are available to assess muscle function and lean and muscle mass, as well as myofiber typing as separate concepts; however, a technical resource unifying these methods is missing. Here, we provide detailed procedures for analyzing muscle function, lean and muscle mass, and myofiber typing in a comprehensive technical resource paper.
Graphical abstract
Forkhead (Fkh/Fox) domain transcription factors (TFs) mediate multiple cardiogenic processes in both mammals and Drosophila. We showed previously that the Drosophila Fox gene jumeau (jumu) controls three categories of cardiac progenitor cell division—asymmetric, symmetric, and cell division at an earlier stage—by regulating Polo kinase activity, and mediates the latter two categories in concert with the TF Myb. Those observations raised the question of whether other jumu-regulated genes also mediate all three categories of cardiac progenitor cell division or a subset thereof. By comparing microarray-based expression profiles of wild-type and jumu loss-of-function mesodermal cells, we identified nebbish (neb), a kinesin-encoding gene activated by jumu. Phenotypic analysis shows that neb is required for only two categories of jumu-regulated cardiac progenitor cell division: symmetric and cell division at an earlier stage. Synergistic genetic interactions between neb, jumu, Myb, and polo and the rescue of jumu mutations by ectopic cardiac mesoderm-specific expression of neb demonstrate that neb is an integral component of a jumu-regulated subnetwork mediating cardiac progenitor cell divisions. Our results emphasize the central role of Fox TFs in cardiogenesis and illustrate how a single TF can utilize different combinations of other regulators and downstream effectors to control distinct developmental processes.
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