Small adipose stores in cystic fibrosis mice are characterized by reduced cell volume, not cell number

Cystic fibrosis (CF) is a lethal genetic disorder that affects many organ systems of the body, including various endocrine and exocrine tissues. Health and survival positively associate with body mass, and as a consequence, CF clinical care includes high-fat, high-calorie diets to maintain and increase adipose tissue stores. Such strategies have been implemented without a clear understanding of the cause and effect relationship between body mass and patients’ health. Here, we used CF mouse models, which display small adipose stores, to begin examining body fat as a prelude into mechanistic studies of low body growth in CF, so that optimal therapeutic strategies could be developed. We reasoned that low adiposity must result from reduced number and/or volume of adipocytes. To determine relative contribution of either mechanism, we quantified volume of intraperitoneal and subcutaneous adipocytes. We found smaller, but not fewer, adipocytes in CF compared with wild-type (WT) animals. Specifically, intraperitoneal CF adipocytes were one-half the volume of WT cells, whereas subcutaneous cells were less affected by the Cftr genotype. No differences were found in cell types between CF and WT adipose tissues. Adipose tissue CFTR mRNA was detected, and we found greater CFTR expression in intraperitoneal depots as compared with subcutaneous samples. RNA sequencing revealed that CF adipose tissue exhibited lower expression of several key genes of adipocyte function ( Lep, Pck1, Fas, Jun), consistent with low triglyceride storage. The data indicate that CF adipocytes contain fewer triglycerides than WT cells, and a role for CFTR in these cells is proposed. NEW & NOTEWORTHY Adipocytes in cystic fibrosis mice exhibit smaller size due to low triglyceride storage. Adipocyte cell number per fat pad is similar, implying triglyceride storage problem. The absence of CFTR function in adipose tissue has been proposed as a direct link to low triglyceride storage in cystic fibrosis.

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Changes in Children’s Body Composition and Posture during Puberty Growth

Children ◽

10.3390/children8040288 ◽

2021 ◽

Vol 8 (4) ◽

pp. 288

Author(s):

Wojciech Rusek ◽

Joanna Baran ◽

Justyna Leszczak ◽

Marzena Adamczyk ◽

Rafał Baran ◽

...

Keyword(s):

Body Composition ◽

Adipose Tissue ◽

Regression Analysis ◽

Body Mass ◽

Pelvic Obliquity ◽

The Body ◽

Body Posture ◽

Older Children ◽

The Difference ◽

The Right

The main goal of our study was to determine how the age of children, puberty and anthropometric parameters affect the formation of body composition and faulty body posture development in children. The secondary goal was to determine in which body segments abnormalities most often occur and how gender differentiates the occurrence of adverse changes in children’s body posture and body composition during puberty. The study group consisted of 464 schoolchildren aged from 6–16. Body posture was assessed with the Zebris system. The composition of the body mass was tested with Tanita MC 780 MA body mass analyzer and the body height was measured using a portable stadiometer PORTSTAND 210. The participants were further divided due to the age of puberty. Tanner division was adopted. The cut-off age for girls is ≥10 years and for boys it is ≥12 years. The analyses applied descriptive statistics, the Pearson correlation, stepwise regression analysis and the t-test. The accepted level of significance was p < 0.05. The pelvic obliquity was lower in older children (beta = −0.15). We also see that age played a significant role in the difference in the height of the right pelvis (beta = −0.28), and the difference in the height of the right shoulder (beta = 0.23). Regression analysis showed that the content of adipose tissue (FAT%) increased with body mass index (BMI) and decreased with increasing weight, age, and height. Moreover, the FAT% was lower in boys than in girls (beta negative equal to −0.39). It turned out that older children (puberty), had greater asymmetry in the right shoulder blade (p < 0.001) and right shoulder (p = 0.003). On the other hand, younger children (who were still before puberty) had greater anomalies in the left trunk inclination (p = 0.048) as well as in the pelvic obliquity (p = 0.008). Girls in puberty were characterized by greater asymmetry on the right side, including the shoulders (p = 0.001), the scapula (p = 0.001) and the pelvis (p < 0.001). In boys, the problem related only to the asymmetry of the shoulder blades (p < 0.001). Girls were characterized by a greater increase in adipose tissue and boys by muscle tissue. Significant differences also appeared in the body posture of the examined children. Greater asymmetry within scapulas and shoulders were seen in children during puberty. Therefore, a growing child should be closely monitored to protect them from the adverse consequences of poor posture or excessive accumulation of adipose tissue in the body.

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The effects of nano-curcumin as a nutritional strategy on clinical and inflammatory factors in children with cystic fibrosis: the study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05224-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Saeedeh Talebi ◽

Mahammad Safarian ◽

Mahmood Reza Jaafari ◽

Seyed Javad Sayedi ◽

Zahra Abbasi ◽

...

Keyword(s):

Cystic Fibrosis ◽

Controlled Trial ◽

Genetic Disorder ◽

The Body ◽

Inflammatory Factors ◽

Secondary Outcome ◽

Nasopharyngeal Swab ◽

Nutritional Strategy ◽

Cftr Protein ◽

The Impact

Abstract Background Cystic fibrosis (CF) is a genetic disorder, which is caused by the CFTR protein defects. Along with CFTR dysfunction, inflammation plays a key role in the disease outcomes. Inflammation may develop due to the internal dysfunction of the CFTR protein or external factors. Curcumin affects the CFTR protein function primarily as a corrector and potentiator and secondary as an anti-inflammatory and antimicrobial agent. The present study aims to assess the impact of nano-curcumin on clinical and inflammatory markers in children with CF. Methods This prospective, double blind control trial will be conducted at the Akbar Children’s Hospital in Mashhad, Iran. Children with CF will be enrolled based on the eligibility criteria. Placebo and curcumin with the maximum dose of 80 mg considering the body surface of the patients will be administrated for 3 months. The primary outcome is to evaluate inflammation based on serum interleukin-6, interleukin-10, and hs-CRP, stool calprotectin, and neutrophil count of nasopharyngeal swab. The secondary outcome involved clinical assessment via spirometry, anthropometrics, and quality of life. They will be assessed before and after 3 months. Discussion Due to the multifarious effects of curcumin on CF disease, it could be proposed as a nutritional strategy in the treatment of cystic fibrosis. Trial registration Iranian Registry of Clinical Trials IRCT20200705048018N1. Registered on July 10, 2020.

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The in vitro secretion of human leptin is gender-dependent but independent of the body mass index of the donors

Acta Endocrinologica ◽

10.1530/eje.0.1430711 ◽

2000 ◽

pp. 711-714 ◽

Cited By ~ 14

Author(s):

C Menendez ◽

R Baldelli ◽

M Lage ◽

X Casabiell ◽

V Pinero ◽

...

Keyword(s):

Body Mass Index ◽

Adipose Tissue ◽

Body Mass ◽

Tissue Sample ◽

Secretory Activity ◽

The Body ◽

Secretory Rate ◽

Omental Adipose Tissue

OBJECTIVE: Leptin is an adipocyte-secreted hormone acting as a signal to the central nervous system, where it regulates energy homeostasis and neuroendocrine processes. Leptin plasma levels are mainly regulated by the percentage of body fat, but are also controlled by several metabolic and nutritional variables. Data regarding leptin secretion suggest that it is gender regulated, and higher levels are present in women than men; however, the biological basis for this sex-related difference is unknown. To clarify those points, a systematic study with tissue cultures from human omental adipose tissue was performed. DESIGN AND METHODS: Surgically obtained samples from 137 patients (68 women, 69 men) were evaluated. The assay was standardized in periods of 24 h ending at 96 h. Each adipose tissue sample from a single donor was incubated in triplicate and leptin results expressed as the mean of the integrated secretion into the medium (nanograms of leptin/g tissue per time). RESULTS: Tissue adipose cultures showed a steady leptin secretion throughout the 96 h studied, with the peak of secretory activity reached at 48 h; afterwards, the in vitro secretion reached a plateau state. Spontaneous leptin secretion in the 24 h and 48 h period, as well as the area under the curve analyzed in the 0-48 h period, showed a gender-based difference that was significantly (P<0. 05) higher in women than in men. When data of spontaneous leptin secretion were correlated with the body mass index (BMI) of the donors, no correlation was found. This suggests that in vivo leptin levels are dependent on the total amount of fat of the individual, but independent of the leptin secretory rate by the adipose tissue of the donor. CONCLUSIONS: Leptin secretion from omental adipose tissue in vitro is: (i) significantly higher in samples from women than in samples from men; and (ii) not correlated with the BMI, showing that in vitro leptin secretion is not related to the adiposity of the donor.

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Anaesthesia in the elderly

10.1093/med/9780199642045.003.0086 ◽

2017 ◽

Author(s):

Bernadette Veering ◽

Chris Dodds

Keyword(s):

Elderly Patients ◽

Postoperative Morbidity ◽

Medical Condition ◽

Clinical Care ◽

The Elderly ◽

Individual Variability ◽

Morbidity And Mortality ◽

Clear Understanding ◽

Organ Systems ◽

Specific Organ

The elderly population continues to grow. As surgical intervention in disease processes becomes more aggressive, the anaesthetist is faced with an increasing number of elderly patients. Elderly patients should be approached with a clear understanding of ageing, how it occurs, how it affects specific organ systems, and how it may influence clinical care, when a patient is subjected to an operation. The ageing process is a multifactorial process, resulting in a decreased capacity for adaptation and producing a gradual decrease in functional reserve of many organ systems. This has significant effects on the physiological responses to surgical and pharmacological trespass faced during anaesthesia. Increasing age is associated with changes in the response to a wide variety of drugs. Changes in dose–response relationships may be as a result of changes in pharmacokinetics, pharmacodynamics, or a combination of both. One should realize that increasing age is associated with a large inter-individual variability in dose requirements. As such, it is important to carefully titrate the dose against the desired clinical effect in an older patient. Preoperative physical and mental state are the most important determinants of per- and postoperative morbidity and mortality. The number of co-morbidities increases with advanced age and as such, optimization of the medical condition is essential to reduce the morbidity and mortality.

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Nimodipine Reappraised: An Old Drug With a Future

Current Neuropharmacology ◽

10.2174/1570159x17666190927113021 ◽

2019 ◽

Vol 18 (1) ◽

pp. 65-82 ◽

Cited By ~ 3

Author(s):

Andrew P. Carlson ◽

Daniel Hänggi ◽

Robert L. Macdonald ◽

Claude W. Shuttleworth

Keyword(s):

Ischemic Stroke ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Clinical Care ◽

Cell Types ◽

Current Data ◽

The Body ◽

Neurological Deficits ◽

Cerebral Vasoconstriction ◽

Voltage Gated Calcium Channels ◽

Dihydropyridine Calcium Channel Antagonist

Nimodipine is a dihydropyridine calcium channel antagonist that blocks the flux of extracellular calcium through L-type, voltage-gated calcium channels. While nimodipine is FDAapproved for the prevention and treatment of neurological deficits in patients with aneurysmal subarachnoid hemorrhage (aSAH), it affects myriad cell types throughout the body, and thus, likely has more complex mechanisms of action than simple inhibition of cerebral vasoconstriction. Newer understanding of the pathophysiology of delayed ischemic injury after a variety of acute neurologic injuries including aSAH, traumatic brain injury (TBI) and ischemic stroke, coupled with advances in the drug delivery method for nimodipine, have reignited interest in refining its potential therapeutic use. In this context, this review seeks to establish a firm understanding of current data on nimodipine’s role in the mechanisms of delayed injury in aSAH, TBI, and ischemic stroke, and assess the extensive clinical data evaluating its use in these conditions. In addition, we will review pivotal trials using locally administered, sustained release nimodipine and discuss why such an approach has evaded demonstration of efficacy, while seemingly having the potential to significantly improve clinical care.

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Cell size is positively correlated between different tissues in passerine birds and amphibians, but not necessarily in mammals

Biology Letters ◽

10.1098/rsbl.2010.0288 ◽

2010 ◽

Vol 6 (6) ◽

pp. 792-796 ◽

Cited By ~ 42

Author(s):

J. Kozłowski ◽

M. Czarnołęski ◽

A. François-Krassowska ◽

S. Maciak ◽

T. Pis

Keyword(s):

Cell Size ◽

Body Mass ◽

Cell Types ◽

Cell Number ◽

Passerine Birds ◽

Mass Scaling ◽

Cellular Models ◽

Mammalian Tissues ◽

Allometric Theory ◽

Different Tissues

We examined cell size correlations between tissues, and cell size to body mass relationships in passerine birds, amphibians and mammals. The size correlated highly between all cell types in birds and amphibians; mammalian tissues clustered by size correlation in three tissue groups. Erythrocyte size correlated well with the volume of other cell types in birds and amphibians, but poorly in mammals. In birds, body mass correlated positively with the size of all cell types including erythrocytes, and in mammals only with the sizes of some cell types. Size of mammalian erythrocytes correlated with body mass only within the most taxonomically uniform group of species (rodents and lagomorphs). Cell volume increased with body mass of birds and mammals to less than 0.3 power, indicating that body size evolved mostly by changes in cell number. Our evidence suggests that epigenetic mechanisms determining cell size relationships in tissues are conservative in birds and amphibians, but less stringent in mammals. The patterns of cell size to body mass relationships we obtained challenge some key assumptions of fractal and cellular models used by allometric theory to explain mass-scaling of metabolism. We suggest that the assumptions in both models are not universal, and that such models need reformulation.

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Two applications of developmental genetics to paleontology: segmentation genes in molluscs and preoral appendages in taxa of uncertain affinity

The Paleontological Society Special Publications ◽

10.1017/s247526220000705x ◽

1992 ◽

Vol 6 ◽

pp. 145-145 ◽

Cited By ~ 1

Author(s):

David K. Jacobs

Keyword(s):

Fossil Record ◽

De Novo ◽

Ectopic Expression ◽

Cell Types ◽

The Body ◽

Developmental Genetics ◽

Switching Function ◽

Developmental Sequence ◽

Homologous Genes ◽

Organ Systems

Resolution of deep evolutionary problems, including the origin of the metazoa and the morphologic evolution of higher taxa within the metazoa, have long been sought in the developmental sequence. Haeckel's gastraea theory is perhaps the best example of this endeavor. Since Haeckel's time it has become apparent that the early evolution of animal life cannot be read directly from the developmental sequence. Ontogeny itself evolves making it difficult to even identify homologies in the early development between many phyla and classes. However, all may not be lost; during metazoan development gene expression must be localized in order to differentiate cell types in the body during development. It is this regionalized transcription and translation to protein product that differentiates cell types, organ systems, and the morphologic features that we can identify in the fossil record. The functional importance of the genes in question, and the fact that portions of the protein products of these genes must bind to DNA in order to perform their switching function, leads to extreme sequence conservation. This permits the identification and comparison of homologous genes important in the development of divergent taxa even after the passage of the entire Phanerozoic. If these genes retain a pattern of expression in development as well as conservation of the DNA sequence, then we can identify a homologous process derived from the development of the shared ancestor of the two taxa.This approach can be used to address the homology of metameric units. Preliminary results indicate that the segmentation gene engrailed is expressed in chiton trochophores in associated with each of the developing plate fields. The engrailed gene is known to control segmentation processes in arthropods and annelids. Evidently the plates in chitons evolved from serial features in a shared ancestor of annelids, arthropods and molluscs. This indicates that the serial features found in molluscs are ancestral (plesiomorphic), and that the evolution of the mollusca has involved the loss or reduction of serial features rather than their de novo evolution in chitons and monoplacophorans as has been suggested by a number of neontologists. The fossil record suggests successive reduction of serial features in molluscs. This paleontological interpretation now finds support in developmental genetics.Developmental genetics also provides a basis for evolution of body plans. Unusual preoral appendages have evolved in chelicerates, Burgess Shale arthropods such as Yohoia and Leanchoilia, and non arthropod forms such as Opabinia and Tullimonstrum. The differentiation of the vertebral column of vertebrates and the segments of arthropods are controlled by homologous genes that are expressed in a anterior to posterior sequence. Out of place (ectopic) expression of posterior genes in the anterior region produces posterior features in the antennal field of arthropods and in the most anterior vertebrae of the vertebrates. This potential for conversion of anterior features was present in the shared ancestor of vertebrates and arthropods. Thus evolution of novel anterior features resulting from ectopic expression could occur in both deuterostomes and protostomes and may account for a range of novel fossil forms. This suggests that parallel evolution of unusual anterior features could occur, and the presence of these features may not be the best character to use in a phylogenetic analyses.

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Alternative Splicing Shapes the Phenotype of a Mutation inBBS8To Cause Nonsyndromic Retinitis Pigmentosa

Molecular and Cellular Biology ◽

10.1128/mcb.00040-15 ◽

2015 ◽

Vol 35 (10) ◽

pp. 1860-1870 ◽

Cited By ~ 23

Author(s):

Daniel Murphy ◽

Ratnesh Singh ◽

Saravanan Kolandaivelu ◽

Visvanathan Ramamurthy ◽

Peter Stoilov

Keyword(s):

Alternative Splicing ◽

Retinitis Pigmentosa ◽

Genetic Disorder ◽

Photoreceptor Cells ◽

Cell Types ◽

The Body ◽

Specific Cell ◽

Cell Type ◽

Multiple Systems ◽

Reading Frame

Bardet-Biedl syndrome (BBS) is a genetic disorder affecting multiple systems and organs in the body. Several mutations in genes associated with BBS affect only photoreceptor cells and cause nonsyndromic retinitis pigmentosa (RP), raising the issue of why certain mutations manifest as a systemic disorder whereas other changes in the same gene affect only a specific cell type. Here, we show that cell-type-specific alternative splicing is responsible for confining the phenotype of the A-to-G substitution in the 3′ splice site ofBBS8exon 2A (IVS1-2A>G mutation) in theBBS8gene to photoreceptor cells. The IVS1-2A>G mutation leads to missplicing ofBBS8exon 2A, producing a frameshift in theBBS8reading frame and thus eliminating the protein specifically in photoreceptor cells. Cell types other than photoreceptors skip exon 2A from the matureBBS8transcript, which renders them immune to the mutation. We also show that the splicing ofBbs8exon 2A in photoreceptors is directed exclusively by redundant splicing enhancers located in the adjacent introns. These intronic sequences are sufficient for photoreceptor-cell-specific splicing of heterologous exons, including an exon with a randomized sequence.

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The anatomy, chemical composition, and metabolism of adipose tissue in wild polar bears (Ursus maritimus)

Canadian Journal of Zoology ◽

10.1139/z92-049 ◽

1992 ◽

Vol 70 (2) ◽

pp. 326-341 ◽

Cited By ~ 60

Author(s):

Caroline M. Pond ◽

Christine A. Mattacks ◽

Richard H. Colby ◽

Malcolm A. Ramsay

Keyword(s):

Adipose Tissue ◽

Fatty Acid Composition ◽

Fatty Acid ◽

Body Mass ◽

Acid Composition ◽

Ursus Maritimus ◽

Superficial Layer ◽

The Body ◽

Polar Bears ◽

Adipocyte Volume

Adipose tissue was dissected completely from 14 polar bears (Ursus maritimus) killed in the southeastern Northwest Territories and northern Manitoba in November 1988. Mean adipocyte volume, collagen content, the activities of hexokinase and phosphofructokinase, and the fatty acid composition of the triacylglycerols were measured in samples of adipose tissue from several superficial, intra-abdominal, and inter-muscular depots homologous to those of other terrestrial mammals. The total adipocyte complement was calculated from the mass of each depot and its site-specific adipocyte volume. All the adipose depots found in other Carnivora and most other mammals are present in polar bears. The superficial layer of adipose tissue in polar bears arises from thickening and lateral expansion of depots that are discrete in most other mammals. All depots except the cardiac adipose tissue expand with increasing fatness, but the superficial depots expand faster than any of the internal depots, almost entirely by adipocyte proliferation. The gross anatomy of the superficial adipose tissue is determined mainly by the effect of body mass on the ratio of the surface area of the body to its volume. The superficial depots account for a greater proportion of the total adipose tissue in larger bears and in fatter specimens. The total adipocyte complement is about two to three times greater than that predicted from allometric equations relating adipocyte complement to body mass in non-arctic carnivores. The fatty acid composition of the triacylglycerols in the adipose tissue of polar bears is similar to that of the milk and the serum, but there were fewer long-chain polyunsaturated fatty acids than in their principal prey, ringed seals. There was no clearcut biochemical evidence for the existence of a thermal gradient between the inner and outer sides of the superficial adipose tissue. We conclude that in spite of their arctic habitat, neither the gross distribution of adipose tissue of polar bears nor its biochemical properties are adapted to thermal insulation. The enlarged superficial layer of adipose tissue is primarily an adaptation to increased energy storage.

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Polyploidy in Cardiomyocytes

Circulation Research ◽

10.1161/circresaha.119.315408 ◽

2020 ◽

Vol 126 (4) ◽

pp. 552-565 ◽

Cited By ~ 14

Author(s):

Wouter Derks ◽

Olaf Bergmann

Keyword(s):

Cardiac Injury ◽

Physiological Role ◽

Cell Types ◽

Cell Number ◽

The Body ◽

Cardiomyocyte Hypertrophy ◽

Heart Regeneration ◽

Cardiomyocyte Proliferation ◽

Hypertrophic Growth

The hallmark of most cardiac diseases is the progressive loss of cardiomyocytes. In the perinatal period, cardiomyocytes still proliferate, and the heart shows the capacity to regenerate upon injury. In the adult heart, however, the actual rate of cardiomyocyte renewal is too low to efficiently counteract substantial cell loss caused by cardiac injury. In mammals, cardiac growth by cell number expansion changes to growth by cardiomyocyte enlargement soon after birth, coinciding with a period in which most cardiomyocytes increase their DNA content by multinucleation and nuclear polyploidization. Although cardiomyocyte hypertrophy is often associated with these processes, whether polyploidy is a prerequisite or a consequence of hypertrophic growth is unclear. Both the benefits of cardiomyocyte enlargement over proliferative growth of the heart and the physiological role of polyploidy in cardiomyocytes are enigmatic. Interestingly, hearts in animal species with substantial cardiac regenerative capacity dominantly comprise diploid cardiomyocytes, raising the hypothesis that cardiomyocyte polyploidy poses a barrier for cardiomyocyte proliferation and subsequent heart regeneration. On the contrary, there is also evidence for self-duplication of multinucleated myocytes, suggesting a more complex picture of polyploidy in heart regeneration. Polyploidy is not restricted to the heart but also occurs in other cell types in the body. In this review, we explore the biological relevance of polyploidy in different species and tissues to acquire insight into its specific role in cardiomyocytes. Furthermore, we speculate about the physiological role of polyploidy in cardiomyocytes and how this might relate to renewal and regeneration.

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