Triglycerides are the major form of stored fat in all animals. One important determinant of whole-body fat storage is whether an animal is male or female. Here, we use Drosophila, an established model for studies on triglyceride metabolism, to gain insight into the genes and physiological mechanisms that contribute to sex differences in fat storage. Our analysis of triglyceride storage and breakdown in both sexes identified a role for triglyceride lipase brummer (bmm) in the regulation of sex differences in triglyceride homeostasis. Normally, male flies have higher levels of bmm mRNA both under normal culture conditions and in response to starvation, a lipolytic stimulus. We find that loss of bmm largely eliminates the sex difference in triglyceride storage and abolishes the sex difference in triglyceride breakdown via strongly male-biased effects. Although we show that bmm function in the fat body affects whole-body triglyceride levels in both sexes, in males, we identify an additional role for bmm function in the somatic cells of the gonad and in neurons in the regulation of whole-body triglyceride homeostasis. Furthermore, we demonstrate that lipid droplets are normally present in both the somatic cells of the male gonad and in neurons, revealing a previously unrecognized role for bmm function, and possibly lipid droplets, in these cell types in the regulation of whole-body triglyceride homeostasis. Taken together, our data reveal a role for bmm function in the somatic cells of the gonad and in neurons in the regulation of male-female differences in fat storage and breakdown and identify bmm as a link between the regulation of triglyceride homeostasis and biological sex.
Sex differences in whole-body fat storage exist in many species. For example, Drosophila females store more fat than males. Yet, the mechanisms underlying this sex difference in fat storage remain incompletely understood. Here, we identify a key role for sex determination gene transformer (tra) in regulating the male-female difference in fat storage. Normally, a functional Tra protein is present only in females, where it promotes female sexual development. We show that loss of Tra in females reduced whole-body fat storage, whereas gain of Tra in males augmented fat storage. Tra's role in promoting fat storage was largely due to its function in neurons, specifically the Adipokinetic hormone (Akh)-producing cells (APCs). Our analysis of Akh pathway regulation revealed a male bias in APC activity and Akh pathway function, where this sex-biased regulation influenced the sex difference in fat storage by limiting triglyceride accumulation in males. Importantly, Tra loss in females increased Akh pathway activity, and genetically manipulating the Akh pathway rescued Tra-dependent effects on fat storage. This identifies sex-specific regulation of Akh as one mechanism underlying the male-female difference in whole-body triglyceride levels, and provides important insight into the conserved mechanisms underlying sexual dimorphism in whole-body fat storage.
In fruit flies, the male-specific fruitless (fru) gene product FruBM plays a central role in establishing the neural circuitry for male courtship behavior by orchestrating the transcription of genes required for the male-type specification of individual neurons. We herein identify the core promoter recognition factor gene Trf2 as a dominant modifier of fru actions. Trf2 knockdown in the sexually dimorphic mAL neurons leads to the loss of a male-specific neurite and a reduction in male courtship vigor. TRF2 forms a repressor complex with FruBM, strongly enhancing the repressor activity of FruBM at the promoter region of the robo1 gene, whose function is required for inhibiting the male-specific neurite formation. In females that lack FruBM, TRF2 stimulates robo1 transcription. Our results suggest that TRF2 switches its own role from an activator to a repressor of transcription upon binding to FruBM, thereby enabling the ipsilateral neurite formation only in males.
Alprazolam is used as an anxiolytic drug for generalized anxiety disorder and it has been reported to produce sedation and anterograde amnesia. In the current study, we randomly divided 26 healthy male volunteers into two groups: one group taking alprazolam 0.5 mg and the other taking placebo daily for two weeks. We utilized the Cambridge Neuropsychological Test Automated Battery (CANTAB) software to assess the chronic effect of alprazolam. We selected Paired Associates Learning (PAL) and Delayed Matching to Sample (DMS) tests for memory, Rapid Visual Information Processing (RVP) for attention, and Choice Reaction Time (CRT) for psychomotor performance twice: before starting the treatment and after the completion of the treatment. We found statistically significant impairment of visual memory in one parameter of PAL and three parameters of DMS in alprazolam group. The PAL mean trial to success and total correct matching in 0-second delay, 4-second delay, and all delay situation of DMS were impaired in alprazolam group. RVP total hits after two weeks of alprazolam treatment were improved in alprazolam group. But such differences were not observed in placebo group. In our study, we found that chronic administration of alprazolam affects memory but attentive and psychomotor performance remained unaffected.
The relationship between the elevated levels of serum malondialdehyde, depleted level of antioxidants (vitamin A, E and C) and altered level of immunoglobulins (IgA, IgG and IgM) in several psychiatric disorders has been established by various experimental evidences over the past few years. But previously no study was carried out to determine these components in patients suffering from generalized anxiety disorder (GAD) in Bangladesh. This study was conducted to compare the serum concentration of these components in GAD patients and healthy volunteers; matched by socioeconomic and sociodemographic parameters. Serum level of malondialdehyde and vitamin C were determined by UV spectrophotometric method, vitamins A and E were detected by RP-HPLC method whereas immunoglobulin levels were determined by turbidimetric method. Data were analyzed by independent t-test, Pearson's correlation and regression analysis. Significantly lower level of vitamin E (p<0.05) and significantly higher level of vitamin C were found in GAD patients than the healthy controls, whereas the change of vitamin A was insignificant. Serum malondialdehyde content was significantly higher (p<0.05) and IgM level was significantly (p<0.05) higher than that of the controls. Change in concentrations of IgG and IgA were insignificant (p>0.05). Pearson's correlation coefficient suggested that there were some significant positive and negative correlations among these tested components. Our study reveals that GAD patients have considerably higher level of malondialdehyde, immunoglobulins and altered level of antioxidant vitamins. These findings may play a key role in the diagnosis and treatment of GAD patients.
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