Sex determination gene transformer regulates the male-female difference in Drosophila fat storage via the adipokinetic hormone pathway

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.

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Faculty Opinions recommendation of Dual lipolytic control of body fat storage and mobilization in Drosophila.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1084902.559303 ◽

2008 ◽

Author(s):

Serap Aksoy

Keyword(s):

Body Fat ◽

Fat Storage

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Determinants of maximal whole-body fat oxidation in elite cross-country skiers: Role of skeletal muscle mitochondria

Scandinavian Journal of Medicine and Science in Sports ◽

10.1111/sms.13298 ◽

2018 ◽

Vol 28 (12) ◽

pp. 2494-2504 ◽

Cited By ~ 14

Author(s):

Sune Dandanell ◽

Anne-Kristine Meinild-Lundby ◽

Andreas B. Andersen ◽

Paul F. Lang ◽

Laura Oberholzer ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Fat ◽

Fat Oxidation ◽

Whole Body ◽

Muscle Mitochondria ◽

Skeletal Muscle Mitochondria ◽

Cross Country

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Increasing skeletal muscle carnitine content in older individuals increases whole‐body fat oxidation during moderate‐intensity exercise

Aging Cell ◽

10.1111/acel.13303 ◽

2021 ◽

Vol 20 (2) ◽

Author(s):

Carolyn Chee ◽

Chris E. Shannon ◽

Aisling Burns ◽

Anna L. Selby ◽

Daniel Wilkinson ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Fat ◽

Fat Oxidation ◽

Whole Body ◽

Moderate Intensity ◽

Older Individuals ◽

Moderate Intensity Exercise

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Sex differences in the associations between adiposity distribution and cardiometabolic risk factors in overweight or obese individuals: a cross-sectional study

BMC Public Health ◽

10.1186/s12889-021-11316-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yide Yang ◽

Ming Xie ◽

Shuqian Yuan ◽

Yuan Zeng ◽

Yanhui Dong ◽

...

Keyword(s):

Risk Factors ◽

Sex Differences ◽

Body Fat ◽

Regression Models ◽

Cardiometabolic Risk ◽

Cardiometabolic Risk Factors ◽

Whole Body ◽

Anthropometric Measurement ◽

Cardiometabolic Health ◽

Lower Odds

Abstract Background We aimed to assess the associations between adiposity distribution and cardiometabolic risk factors among overweight and obese adults in China, and to demonstrate the sex differences in these associations. Methods A total of 1221 participants (455 males and 766 females) were included in this study. Percentage of body fat (PBF) of the whole body and regional areas, including arm, thigh, trunk, android, and gynoid, were measured by the dual-energy X-ray absorptiometry method. Central adiposity was measured by waist circumference. Clustered cardiometabolic risk was defined as the presence of two or more of the six cardiometabolic risk factors, namely, high triglyceride, low high density lipoprotein, elevated glucose, elevated blood pressure, elevated high sensitivity C-reactive protein, and low adiponectin. Linear regression models and multivariate logistic regression models were used to assess the associations between whole body or regional PBF and cardiometabolic risk factors. Results In females, except arm adiposity, other regional fat (thigh, trunk, android, gynoid) and whole-body PBF are significantly associated with clustered cardiometabolic risk, adjusting for age, smoking, alcohol drinking, physical activity, and whole-body PBF. One-SD increase in Z scores of the thigh and gynoid PBF were significantly associated with 80 and 78% lower odds of clustered cardiometabolic risk (OR: 0.20, 95%CI: 0.12–0.35 and OR: 0.22, 95%CI: 0.12–0.41). Trunk, android and whole-body PBF were significantly associated with higher odds of clustered risk with OR of 1.90 (95%CI:1.02–3.55), 2.91 (95%CI: 1.75–4.85), and 2.01 (95%CI: 1.47–2.76), respectively. While in males, one-SD increase in the thigh and gynoid PBF are associated with 94% (OR: 0.06, 95%CI: 0.02–0.23) and 83% lower odds (OR: 0.17, 95%CI: 0.05–0.57) of clustered cardiometabolic risk, respectively. Android and whole-body PBF were associated with higher odds of clustered cardiometabolic risk (OR: 3.39, 95%CI: 1.42–8.09 and OR: 2.45, 95%CI: 1.53–3.92), but the association for trunk PBF was not statistically significant (OR: 1.16, 95%CI: 0.42–3.19). Conclusions Adiposity distribution plays an important role in the clustered cardiometabolic risk in participants with overweight and obese and sex differences were observed in these associations. In general, central obesity (measured by android PBF) could be the best anthropometric measurement for screening people at risk for CVD risk factors for both men and women. Upper body fat tends to be more detrimental to cardiometabolic health in women than in men, whereas lower body fat is relatively more protective in men than in women.

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Tissue-specific expression of Sprouty1 in mice protects against high-fat diet-induced fat accumulation, bone loss and metabolic dysfunction

British Journal Of Nutrition ◽

10.1017/s0007114511006209 ◽

2011 ◽

Vol 108 (6) ◽

pp. 1025-1033 ◽

Cited By ~ 7

Author(s):

Sumithra Urs ◽

Terry Henderson ◽

Phuong Le ◽

Clifford J. Rosen ◽

Lucy Liaw

Keyword(s):

Adipose Tissue ◽

Bone Loss ◽

Bone Mass ◽

Body Fat ◽

High Fat Diet ◽

Conditional Knockout ◽

Whole Body ◽

High Fat ◽

Tissue Specific ◽

Diet Induced Obesity

We recently characterised Sprouty1 (Spry1), a growth factor signalling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue-specific Spry1 expression in mice resulted in increased bone mass and reduced body fat, while conditional knockout of Spry1 had the opposite effect with decreased bone mass and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high-fat diet-induced obesity, bone loss and associated lipid abnormalities, and demonstrate that Spry1 has a long-term protective effect on mice fed a high-energy diet. We studied diet-induced obesity in mice with fatty acid binding promoter-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole-body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1-null mice, a high-fat diet increased body fat by 40 %, impaired glucose regulation and led to liver steatosis. However, overexpression of Spry1 led to 35 % (P < 0·05) lower body fat, reduced bone loss and normal metabolic function compared with single transgenics. This protective phenotype was associated with decreased circulating insulin (70 %) and leptin (54 %; P < 0·005) compared with controls on a high-fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45 %. We show that conditional Spry1 expression in adipose tissue protects against high-fat diet-induced obesity and associated bone loss.

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Whole body fat: Content and distribution

Progress in Nuclear Magnetic Resonance Spectroscopy ◽

10.1016/j.pnmrs.2013.04.001 ◽

2013 ◽

Vol 73 ◽

pp. 56-80 ◽

Cited By ~ 69

Author(s):

E.L. Thomas ◽

J.A. Fitzpatrick ◽

S.J. Malik ◽

S.D. Taylor-Robinson ◽

J.D. Bell

Keyword(s):

Body Fat ◽

Fat Content ◽

Whole Body ◽

Body Fat Content

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Body Composition, Dietary Intake, and Iron Status of Female Collegiate Swimmers and Divers

International Journal of Sport Nutrition and Exercise Metabolism ◽

10.1123/ijsnem.16.3.281 ◽

2006 ◽

Vol 16 (3) ◽

pp. 281-295 ◽

Cited By ~ 12

Author(s):

Heidi L. Petersen ◽

C. Ted Peterson ◽

Manju B. Reddy ◽

Kathy B. Hanson ◽

James H. Swain ◽

...

Keyword(s):

Body Composition ◽

Dietary Intake ◽

Body Fat ◽

Lean Mass ◽

Iron Status ◽

Dietary Quality ◽

Whole Body ◽

Vitamin B ◽

Percentage Body Fat ◽

X Ray

This study determined the effect of training on body composition, dietary intake, and iron status of eumenorrheic female collegiate swimmers (n = 18) and divers (n = 6) preseason and after 16 wk of training. Athletes trained on dryland (resistance, strength, fexibility) 3 d/wk, 1.5 h/d and in-water 6 d/wk, nine, 2-h sessions per week (6400 to 10,000 kJ/d). Body-mass index (kg/m2; P = 0.05), waist and hip circumferences (P ≤ 0.0001), whole body fat mass (P = 0.0002), and percentage body fat (P ≤ 0.0001) decreased, whereas lean mass increased (P = 0.028). Using dual-energy X-ray absorptiometry, we found no change in regional lean mass, but fat decreased at the waist (P = 0.0002), hip (P = 0.0002), and thigh (P = 0.002). Energy intake (10,061 ± 3617 kJ/d) did not change, but dietary quality improved with training, as refected by increased intakes of fber (P = 0.036), iron (P = 0.015), vitamin C (P = 0.029), vitamin B-6 (P = 0.032), and fruit (P = 0.003). Iron status improved as refected by slight increases in hemoglobin (P = 0.046) and hematocrit (P = 0.014) and decreases in serum transferrin receptor (P ≤ 0.0001). Studies are needed to further evaluate body composition and iron status in relation to dietary intake in female swimmers.

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Systemic nicotine alters whole-body fat utilization in female rats

Physiology & Behavior ◽

10.1016/j.physbeh.2003.10.011 ◽

2004 ◽

Vol 80 (4) ◽

pp. 563-567 ◽

Cited By ~ 25

Author(s):

Christopher Bishop ◽

Graham C. Parker ◽

Donald V. Coscina

Keyword(s):

Body Fat ◽

Female Rats ◽

Whole Body ◽

Fat Utilization

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Induction of female Sex-lethal RNA splicing in male germ cells: implications for Drosophila germline sex determination

Development ◽

10.1242/dev.124.24.5033 ◽

1997 ◽

Vol 124 (24) ◽

pp. 5033-5048 ◽

Cited By ~ 7

Author(s):

J.H. Hager ◽

T.W. Cline

Keyword(s):

Sex Determination ◽

Germ Cells ◽

Rna Splicing ◽

Feedback Loop ◽

Dose Effect ◽

Male Germ Cells ◽

Control Female ◽

Sex Lethal ◽

Specific Regulation ◽

Female Specific

With a focus on Sex-lethal (Sxl), the master regulator of Drosophila somatic sex determination, we compare the sex determination mechanism that operates in the germline with that in the soma. In both cell types, Sxl is functional in females (2X2A) and nonfunctional in males (1X2A). Somatic cell sex is determined initially by a dose effect of X:A numerator genes on Sxl transcription. Once initiated, the active state of SXL is maintained by a positive autoregulatory feedback loop in which Sxl protein insures its continued synthesis by binding to Sxl pre-mRNA and thereby imposing the productive (female) splicing mode. The gene splicing-necessary factor (snf), which encodes a component of U1 and U2 snRNPs, participates in this RNA splicing control. Here we show that an increase in the dose of snf+ can trigger the female Sxl RNA splicing mode in male germ cells and can feminize triploid intersex (2X3A) germ cells. These snf+ dose effects are as dramatic as those of X:A numerator genes on Sxl in the soma and qualify snf as a numerator element of the X:A signal for Sxl in the germline. We also show that female-specific regulation of Sxl in the germline involves a positive autoregulatory feedback loop on RNA splicing, as it does in the soma. Neither a phenotypically female gonadal soma nor a female dose of X chromosomes in the germline is essential for the operation of this feedback loop, although a female X-chromosome dose in the germline may facilitate it. Engagement of the Sxl splicing feedback loop in somatic cells invariably imposes female development. In contrast, engagement of the Sxl feedback loop in male germ cells does not invariably disrupt spermatogenesis; nevertheless, it is premature to conclude that Sxl is not a switch gene in germ cells for at least some sex-specific aspects of their differentiation. Ironically, the testis may be an excellent organ in which to study the interactions among regulatory genes such as Sxl, snf, ovo and otu which control female-specific processes in the ovary.

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