Tissue-specific responses that constrain glucose oxidation and increase lactate production with the severity of hypoxemia in fetal sheep.

Fetal hypoxemia decreases insulin and increases cortisol and norepinephrine concentrations and may restrict growth by decreasing glucose utilization and altering substrate oxidation. Specifically, we hypothesized that hypoxemia would decrease fetal glucose oxidation and increase lactate and pyruvate production. We tested this by measuring whole body glucose oxidation and lactate production, and molecular pathways in liver, muscle, adipose, and pancreas tissues of fetuses exposed to maternal hypoxemia for 9 days (HOX) compared with control fetal sheep (CON) in late gestation. Fetuses with more severe hypoxemia had lower whole body glucose oxidation rates, and HOX fetuses had increased lactate production from glucose. In muscle and adipose tissue, expression of the glucose transporter GLUT4 was decreased. In muscle, pyruvate kinase (PKM) and lactate dehydrogenase B (LDHB) expression was decreased. In adipose tissue, LDHA and lactate transporter (MCT1) expression was increased. In liver, there was decreased gene expression of PKLR and MPC2 and phosphorylation of PDH, and increased LDHA gene and LDH protein abundance. LDH activity, however, was decreased only in HOX skeletal muscle. There were no differences in basal insulin signaling across tissues, nor differences in pancreatic tissue insulin content, ß-cell area, or genes regulating ß-cell function. Collectively, these results demonstrate coordinated metabolic responses across tissues in the hypoxemic fetus that limit glucose oxidation and increase lactate and pyruvate production. These responses may be mediated by hypoxemia-induced endocrine responses including increased norepinephrine and cortisol, which inhibit pancreatic insulin secretion resulting in lower insulin concentrations and decreased stimulation of glucose utilization.NEW & NOTEWORTHY Hypoxemia lowered fetal glucose oxidation rates, based on severity of hypoxemia, and increased lactate production. This was supported by tissue-specific metabolic responses that may result from increased norepinephrine and cortisol concentrations, which decrease pancreatic insulin secretion and insulin concentrations and decrease glucose utilization. This highlights the vulnerability of metabolic pathways in the fetus and demonstrates that constrained glucose oxidation may represent an early event in response to sustained hypoxemia and fetal growth restriction.

Body-fat sensor triggers ribosome maturation in the steroidogenic gland to initiate sexual maturation in Drosophila.

Fat stores are critical for reproductive success and may govern maturation initiation. Here, we report that signaling and sensing fat sufficiency for sexual maturation commitment requires the lipid carrier apolipophorin in fat cells and Sema1a in the neuroendocrine prothoracic gland (PG). Larvae lacking apolpp or Sema1a fail to initiate maturation despite accruing sufficient fat stores, and they continue gaining weight until death. Mechanistically, sensing peripheral body-fat levels via the apolipophorin/Sema1a axis regulates endocytosis, endoplasmic reticulum remodeling, and ribosomal maturation for the acquisition of the PG cells' high biosynthetic and secretory capacity. Downstream of apolipophorin/Sema1a, leptin-like upd2 triggers the cessation of feeding and initiates sexual maturation. Human Leptin in the insect PG substitutes for upd2, preventing obesity and triggering maturation downstream of Sema1a. These data show how peripheral fat levels regulate the control of the maturation decision-making process via remodeling of endomembranes and ribosomal biogenesis in gland cells.

Inhibition of phosphodiesterase type 9 reduces obesity and cardiometabolic syndrome in mice.

Central obesity with cardiometabolic syndrome (CMS) is a major global contributor to human disease, and effective therapies are needed. Here, we show that cyclic GMP-selective phosphodiesterase 9A inhibition (PDE9-I) in both male and ovariectomized female mice suppresses preestablished severe diet-induced obesity/CMS with or without superimposed mild cardiac pressure load. PDE9-I reduces total body, inguinal, hepatic, and myocardial fat; stimulates mitochondrial activity in brown and white fat; and improves CMS, without significantly altering activity or food intake. PDE9 localized at mitochondria, and its inhibition in vitro stimulated lipolysis in a PPARα-dependent manner and increased mitochondrial respiration in both adipocytes and myocytes. PPARα upregulation was required to achieve the lipolytic, antiobesity, and metabolic effects of PDE9-I. All these PDE9-I-induced changes were not observed in obese/CMS nonovariectomized females, indicating a strong sexual dimorphism. We found that PPARα chromatin binding was reoriented away from fat metabolism-regulating genes when stimulated in the presence of coactivated estrogen receptor-α, and this may underlie the dimorphism. These findings have translational relevance given that PDE9-I is already being studied in humans for indications including heart failure, and efficacy against obesity/CMS would enhance its therapeutic utility.

Accelerated developmental adipogenesis programs adipose tissue dysfunction and cardiometabolic risk in offspring born to dams with metabolic dysfunction.

This study determined if a perturbation in in utero adipogenesis leading to later life adipose tissue (AT) dysfunction underlies programming of cardiometabolic risk in offspring born to dams with metabolic dysfunction. Female mice heterozygous for the leptin receptor deficiency (Hetdb) had 2.4-fold higher prepregnancy fat mass and in late gestation had higher plasma insulin and triglycerides compared with wild-type (Wt) females (P < 0.05). To isolate the role of the intrauterine milieu, wild-type (Wt) offspring from each pregnancy were studied. Differentiation potential in isolated progenitors and cell size distribution analysis revealed accelerated adipogenesis in Wt pups born to Hetdb dams, accompanied by a higher accumulation of neonatal fat mass. In adulthood, whole body fat mass by NMR was higher in male (69%) and female (20%) Wt offspring born to Hetdb versus Wt pregnancies, along with adipocyte hypertrophy and hyperlipidemia (all P < 0.05). Lipidomic analyses by gas chromatography revealed an increased lipogenic index (16:0/18:2n6) after high-fat/fructose diet (HFFD). Postprandial insulin, ADIPO-IR, and ex vivo AT lipolytic responses to isoproterenol were all higher in Wt offspring born to Hetdb dams (P < 0.05). Intrauterine metabolic stimuli may direct a greater proportion of progenitors toward terminal differentiation, thereby predisposing to hypertrophy-induced adipocyte dysfunction.NEW & NOTEWORTHY This study reveals that accelerated adipogenesis during the perinatal window of adipose tissue development predisposes to later life hypertrophic adipocyte dysfunction, thereby compromising the buffering function of the subcutaneous depot.

Thermogenic Fat: Development, Physiological Function, and Therapeutic Potential.

The concerning worldwide increase of obesity and chronic metabolic diseases, such as T2D, dyslipidemia, and cardiovascular disease, motivates further investigations into preventive and alternative therapeutic approaches. Over the past decade, there has been growing evidence that the formation and activation of thermogenic adipocytes (brown and beige) may serve as therapy to treat obesity and its associated diseases owing to its capacity to increase energy expenditure and to modulate circulating lipids and glucose levels. Thus, understanding the molecular mechanism of brown and beige adipocytes formation and activation will facilitate the development of strategies to combat metabolic disorders. Here, we provide a comprehensive overview of pathways and players involved in the development of brown and beige fat, as well as the role of thermogenic adipocytes in energy homeostasis and metabolism. Furthermore, we discuss the alterations in brown and beige adipose tissue function during obesity and explore the therapeutic potential of thermogenic activation to treat metabolic syndrome.

Adipose tissue in health and disease.

Adipose, or fat, tissue (AT) was once considered an inert tissue that primarily existed to store lipids, and was not historically recognized as an important organ in the regulation and maintenance of health. With the rise of obesity and more rigorous research, AT is now recognized as a highly complex metabolic organ involved in a host of important physiological functions, including glucose homeostasis and a multitude of endocrine capabilities. AT dysfunction has been implicated in several disease states, most notably obesity, metabolic syndrome and type 2 diabetes. The study of AT has provided useful insight in developing strategies to combat these highly prevalent metabolic diseases. This review highlights the major functions of adipose tissue and the consequences that can occur when disruption of these functions leads to systemic metabolic dysfunction.

Prediction of the Secretome and the Surfaceome: A Strategy to Decipher the Crosstalk between Adipose Tissue and Muscle during Fetal Growth.

Crosstalk between adipose and muscular tissues is hypothesized to regulate the number of muscular and adipose cells during fetal growth, with post-natal consequences on lean and fat masses. Such crosstalk largely remains, however, to be described. We hypothesized that a characterization of the proteomes of adipose and muscular tissues from bovine fetuses may enhance the understanding of the crosstalk between these tissues through the prediction of their secretomes and surfaceomes. Proteomic experiments have identified 751 and 514 proteins in fetal adipose tissue and muscle. These are mainly involved in the regulation of cell proliferation or differentiation, but also in pathways such as apoptosis, Wnt signalling, or cytokine-mediated signalling. Of the identified proteins, 51 adipokines, 11 myokines, and 37 adipomyokines were predicted, together with 26 adipose and 13 muscular cell surface proteins. Analysis of protein-protein interactions suggested 13 links between secreted and cell surface proteins that may contribute to the adipose-muscular crosstalk. Of these, an interaction between the adipokine plasminogen and the muscular cell surface alpha-enolase may regulate the fetal myogenesis. The in silico secretome and surfaceome analyzed herein exemplify a powerful strategy to enhance the elucidation of the crosstalk between cell types or tissues.

Limitation of adipose tissue by the number of embryonic progenitor cells.

Adipogenesis in adulthood replaces fat cells that turn over and can contribute to the development of obesity. However, the proliferative potential of adipocyte progenitors in vivo is unknown (Faust et al., 1976; Faust et al., 1977; Hirsch and Han, 1969; Johnson and Hirsch, 1972). We addressed this by injecting labeled wild-type embryonic stem cells into blastocysts derived from lipodystrophic A-ZIP transgenic mice, which have a genetic block in adipogenesis. In the resulting chimeric animals, wild-type ES cells are the only source of mature adipocytes. We found that when chimeric animals were fed a high-fat-diet, animals with low levels of chimerism showed a significantly lower adipose tissue mass than animals with high levels of chimerism. The difference in adipose tissue mass was attributed to variability in the amount of subcutaneous adipose tissue as the amount of visceral fat was independent of the level of chimerism. Our findings thus suggest that proliferative potential of adipocyte precursors is limited and can restrain the development of obesity.

miR-760 exerts an antioncogenic effect in esophageal squamous cell carcinoma by negatively driving fat metabolism via targeting c-Myc.

miR-760 is downregulated in various human tumors, and fat metabolism disorder correlates with tumor progression, especially anomalism of key fat metabolic enzymes that are positively modulated by c-Myc. The aim of our study is to elucidate the presumptive molecular mechanisms of miR-760-mediated esophageal squamous cell carcinoma (ESCC) cell function and to assess the therapeutic significance of miR-760 in ESCC patients. Quantitative real-time PCR (RT-qPCR) analysis indicated that miR-760 was significantly downexpressed in ESCC tissues and cell lines. Cell counting kit-8 (CCK-8) assay, colony formation assay, transwell assay, and flow cytometry denoted that induced ectopic overexpression of miR-760 dramatically inhibited ESCC cells proliferation, attenuated migration, and invasion facilitated apoptosis in vitro. Mechanistically, c-Myc predicted using bioinformatics was identified as a potential target gene of miR-760 by luciferase reporter assay. Furthermore, mRNA and protein expression levels of c-Myc and key fat metabolic enzymes were downregulated with miR-760 mimics. The above investigation results, responsible for the antineoplastic properties of miR-760 in ESCC, preliminarily highlighted that the hypothetical signal amongst miR-760, c-Myc, and key fat metabolic enzymes may develop a novel diagnostic marker, therapeutic target, and independent prognostic indicator.

Transgenerational Effects of Periconception Heavy Metal Administration on Adipose Weight and Glucose Homeostasis in Mice at Maturity.

We previously demonstrated that periconception maternal administration (2 mg/kg body weight each) of cadmium chloride (CdCl2) plus methylmercury (II) chloride (CH3HgCl) impaired glucose homeostasis and increased body weights and abdominal adipose tissue weight of male offspring in the F1 generation. However, transgenerational effects of this exposure have not been studied. Therefore, the effects of periconception Cd+Hg administration on indices of chronic diseases at adulthood in F2-F4 generations were examined. Male and female progeny of Cd+Hg periconceptionally treated females, and offspring of vehicle control females were bred with naïve CD1 mice to obtain F2 offspring, with additional crosses as above to the F4 generation (F1-F4 animals were not administered Cd+Hg). Birth weights and litter size were similar in all generations. Indices of impaired glucose homeostasis were observed in matrilineally descended F2 male offspring, including reduced glucose tolerance, along with increased basal phosphorylation of insulin receptor substrate 1 (IRS1) at serine 307 suggesting altered insulin signaling. Reduced glucose tolerance was also seen in F4 males. Increased body weight and/or abdominal adiposity were observed through the F4 generation in males descended matrilineally from the treated female progenitors. Patrilineally derived F2 females displayed reduced glucose tolerance. Females (F2) patrilineally and matrilineally derived displayed significant kidney enlargement. Periconception administration of cadmium and mercury caused persistent transgenerational effects in offspring through the F4 generation in the absence of continued toxicant exposure, with persistent transgenerational effects inherited specifically through the matrilineal germline.

Can we remove scar and fibrosis from adult human myocardium?

The pathological processes leading to heart failure are characterized by the formation of fibrosis and scar, yet the dynamics of scar production and removal are incompletely understood. Spontaneous disappearance of myocardial collagen is reported in infancy but doubted in adulthood where scar volume constitutes a better prognostic indicator than the conventional parameters of ventricular function. Whilst certain drugs are known to attenuate myocardial fibrosis evidence is emerging that stem cell therapy also has the potential to reduce scar size and improve myocardial viability. Both animal studies and clinical trials support the concept that, as in infancy, cellular processes can be triggered to remove collagen and regenerate injured myocardium. The molecular mechanisms likely involve anti-fibrotic cytokines growth factors and matrix-metalloproteinases. Autologous cardiac, bone-marrow and adipose tissue derived stem cells have each shown efficacy. Specific immune privileged mesenchymal stem cells and genetically modified immunomodulatory progenitor cells may in turn provide an allogenic source for the paracrine effects. Thus autologous and allogenic cells both have the potential through paracrine action to reduce scar volume, boost angiogenesis and improve ventricular morphology. The potential benefit of myocardial cell therapy for routine treatment of heart failure is an area that requires further study.

Analysis of correlations between the placental expression of glucose transporters GLUT-1, GLUT-4 and GLUT-9 and selected maternal and fetal parameters in pregnancies complicated by diabetes mellitus.

PURPOSE: The aim of the study was to analyze the correlations between the expression of glucose transporters GLUT-1, GLUT-4, and GLUT-9 in human term placenta and selected maternal and fetal parameters in pregnancies complicated by diabetes mellitus (DM). MATERIALS AND METHODS: Placental samples were obtained from healthy control (n = 25) and diabetic pregnancies, including diet-controlled gestational diabetes mellitus (GDMG1) (n = 16), insulin-controlled gestational diabetes mellitus (GDMG2) (n = 6), and pregestational DM (PGDM) (n = 6). Computer-assisted quantitative morphometry of stained placental sections was performed to determine the expression of selected glucose transporter proteins. For the purposes of correlation analysis, the following parameters were selected: type of diabetes, gestational age, maternal prepregnancy body mass index (BMI), gestational weight gain, third trimester glycated hemoglobin concentration, placental weight, fetal birth weight (FBW) as well as ultrasonographic indicators of fetal adiposity, including subscapular (SSFM), abdominal (AFM), and midthigh (MTFM) fat mass measurements. RESULTS: In the PGDM group, the analysis demonstrated positive correlations between the placental expression of GLUT-1, GLUT-4, and GLUT-9 and FBW, AFM, and SSFM measurements (p < .05). Similarly in the GDMG2 patients positive correlations between GLUT-4 expression, FBW and SSFM were observed (p < .05). In the multivariate regression analysis, only the type of diabetes and FBW were significantly associated with GLUTs expression (p < .001). In addition, maternal prepregnancy BMI significantly contributed to GLUT-1 expression (p < .001). CONCLUSIONS: The study results revealed that placental expression of GLUT-1, GLUT-4, and GLUT-9 may be involved in the intensification of the fetal growth in pregnancies complicated by GDM/PGDM.

Transgenerational Epigenetic Mechanisms in Adipose Tissue Development.

An adverse nutritional environment during the perinatal period increases the risk of adult-onset metabolic diseases, such as obesity, which may persist across generations. Adipose tissue (AT) from offspring of malnourished dams has been shown to display altered adipogenesis, lipogenesis, and adipokine expression, impaired thermogenesis, and low-grade inflammation. Although the exact mechanisms underlying these alterations remain unclear, epigenetic processes are believed to have an important role. In this review, we focus on epigenetic mechanisms in AT that may account for transgenerational dysregulation of adipocyte formation and adipose function. Understanding the complex interactions between maternal diet and epigenetic regulation of the AT in offspring may be valuable in improving preventive strategies against the obesity pandemic.

Embryologic and Fetal Development of the Human Orbit.

PURPOSE: To review the recent data about orbital development and sort out the controversies from the very early stages during embryonic life till final maturation of the orbit late in fetal life, and to appreciate the morphogenesis of all the definitive structures in the orbit in a methodical and timely fashion. METHODS: The authors extensively review major studies detailing every aspect of human embryologic and fetal orbital morphogenesis including the development of extraocular muscles, orbital fat, vessels, nerves, and the supportive connective tissue framework as well as bone. These interdisciplinary studies span almost a century and a half, and include some significant controversial opposing points of view which the authors hopefully sort out. The authors also highlight a few of the most noteworthy molecular biologic studies regarding the multiple and interacting signaling pathways involved in regulating normal orbital morphogenesis. RESULTS: Orbital morphogenesis involves a successive series of subtle yet tightly regulated morphogenetic events that could only be explained through the chronological narrative used by the authors. The processes that trigger and contribute to the formation of the orbits are complex and seem to be intricately regulated by multifaceted interactions and bidirectional cross-talk between a multitude of cellular building raw materials including the developing optic vesicles, neuroectoderm, cranial neural crest cells and mesoderm. CONCLUSIONS: Development of the orbit is a collective enterprise necessitating interactions between, as well as contributions from different cell populations both within and beyond the realm of the orbit. A basic understanding of the processes underlying orbital ontogenesis is a crucial first step toward establishing a genetic basis or an embryologic link with orbital disease.

A mesodermal fate map for adipose tissue.

The embryonic origin of distinct fat depots and the role for ontogeny in specifying the functional differences among adipocyte lineages between and within depots is unclear. Using a Cre/Lox-based strategy to track the fate of major mesodermal subcompartments in mice we present evidence that <50% of interscapular brown adipocytes are derived from progenitors of the central dermomyotome. Furthermore, we demonstrate that depot-specific adipocyte lineages spatially diverge as early as gastrulation, and that perigonadal adipocytes arise from separate mesodermal subcompartments in males and females. Last, we show adipocyte precursors (APs) of distinct lineages within the same depot exhibit indistinguishable responses to a high fat diet, indicating that ontogenetic differences between APs do not necessarily correspond to functional differences in this context. Altogether, these findings shed light on adipose tissue patterning and suggest that the behavior of adipocyte lineage cells is not strictly determined by developmental history.

Gestational Hypoxia and Developmental Plasticity.

Hypoxia is one of the most common and severe challenges to the maintenance of homeostasis. Oxygen sensing is a property of all tissues, and the response to hypoxia is multidimensional involving complicated intracellular networks concerned with the transduction of hypoxia-induced responses. Of all the stresses to which the fetus and newborn infant are subjected, perhaps the most important and clinically relevant is that of hypoxia. Hypoxia during gestation impacts both the mother and fetal development through interactions with an individual's genetic traits acquired over multiple generations by natural selection and changes in gene expression patterns by altering the epigenetic code. Changes in the epigenome determine "genomic plasticity," i.e., the ability of genes to be differentially expressed according to environmental cues. The genomic plasticity defined by epigenomic mechanisms including DNA methylation, histone modifications, and noncoding RNAs during development is the mechanistic substrate for phenotypic programming that determines physiological response and risk for healthy or deleterious outcomes. This review explores the impact of gestational hypoxia on maternal health and fetal development, and epigenetic mechanisms of developmental plasticity with emphasis on the uteroplacental circulation, heart development, cerebral circulation, pulmonary development, and the hypothalamic-pituitary-adrenal axis and adipose tissue. The complex molecular and epigenetic interactions that may impact an individual's physiology and developmental programming of health and disease later in life are discussed.

Increased fetal epicardial fat thickness: A novel ultrasound marker for altered fetal metabolism in diabetic pregnancies.

OBJECTIVE: To evaluate whether fetal epicardial fat thickness (EFT) differs in diabetic and nondiabetic pregnant women. METHODS: Retrospective case-control study of pregnancies between 24 and 36 weeks complicated by preexisting (PDM) or gestational (GDM) diabetes mellitus, matched one to one with controls for body mass index and gestational age (GA). Epicardial fat was identified as the hypoechogenic area between myocardium and visceral pericardium over the right ventricle and its thickness was measured by a single observer blinded to clinical condition and outcomes. A linear regression analysis was performed to assess the relationship between GA and EFT, and regression lines were compared between diabetics and controls. RESULTS: 53 PDM and 53 GDM pregnant women were matched with controls. With the exception of maternal age, the demographics were similar among groups. EFT increased significantly with advancing gestation in both diabetics and controls (P < 0.0001) and was significantly greater in diabetics than in controls (P < 0.0001). The best fit lines were different between diabetics (EFT = 0.05 × GA + 0.07 mm; R2 = 0.70) and controls (EFT = 0.07 × GA + 0.04 mm; R2 = 0.93) (P < 0.0001). CONCLUSION: Fetal EFT was greater in diabetics than in nondiabetics, and even greater in pregestational diabetics. EFT maybe an additional and/or earlier marker to identify early changes in fetal metabolism before accelerated fetal growth and polyhydramnios is apparent.

Preliminary evaluation of foetal liver volume by three-dimensional ultrasound in women with gestational diabetes mellitus.

The aim of the study was to assess the standard foetal biometric measurements and foetal liver volume (FLV) in pregnancies complicated by gestational diabetes mellitus (GDM) at the time of GDM screening and to compare the results with foetuses in normal pregnancies. Ninety-seven pregnant women with normal singleton uncomplicated pregnancies between 24 and 28 weeks of gestation were allocated into GDM (+) (n: 33) and GDM (-) (n: 64) groups based on their 75 g oral glucose tolerance test results. Foetal biometric measurements and FLV measurements of the groups were compared. Although there were no significant differences in the standard biometric measurements between the two groups, FLV was significantly higher in the women with GDM (p < .01). The ROC analysis implied that with a cut-off value of FLV of 32.72 cm3 for GDM prediction, the sensitivity was 78.8% and specificity was 56.3%. We suggest that FLV measurements during the second-trimester ultrasound scanning may be a tool for the prediction of GDM in the obstetric population. Impact statement What is already known on this subject? GDM is an important pregnancy disease, because of its possible foetal and maternal complications. Besides the standard biometric measurements, some other foetal body dimensions such as the anterior abdominal wall thickness, skinfold thickness, adipose tissue thickness, Wharton's jelly thickness, foetal liver length and foetal liver volume (FLV) have been evaluated as ultrasound parameters of glycaemic control. While the evaluation of foetal liver dimensions has a role in identifying foetal growth acceleration, previous studies addressed patients with insulin-dependent diabetes mellitus rather than gestational diabetes mellitus, utilised two-dimensional ultrasound and did not argue the diagnostic value of these findings. What do the results of this study add? In our study, besides the standard biometric measurements, the FLV measurements were evaluated by a three-dimensional ultrasound. Although there were no significant differences in the standard biometric measurements between the GDM (+) and GDM (-) groups, the FLV was significantly higher in women with GDM. The FLV was found to be a potential predictive factor for GDM. The ROC analysis implied that as a cut-off value of FLV of 32.72 cm3 for GDM prediction, the sensitivity was 78.8% and the specificity was 56.3%. What are the implications of these findings for clinical practise and/or further research? Screening for GDM with oral glucose tolerance test within the limited weeks of gestation may not always be feasible. On the other hand, the mid-trimester ultrasound scanning is done almost in all pregnancies. Accordingly, FLV measurement might be an alternative method for the GDM diagnosis.

Quantification of fetal organ volume and fat deposition following in utero exposure to maternal Western Diet using MRI.

PURPOSE: To examine the feasibility of using MRI to identify differences in liver size and fat deposition in fetal guinea pigs exposed to an in utero environment influenced by maternal consumption of a Western diet. MATERIALS AND METHODS: Female guinea pigs fed either an energy-dense Western Diet (WD), comprised of increased saturated fats and simple sugars, or a Control Diet (CD) from weaning through pregnancy, underwent MR scanning near term (~ 60 days; term ~ 69 days). Maternal weights were collected at mating and at MR scanning. T1-weighted, T2-weighted, and IDEAL water-fat images were acquired at 3 Tesla. The images were used to segment maternal adipose tissue, fetal liver, fetal brain, fetal adipose tissue, and total fetal volumes and to measure maternal and fetal hepatic fat fractions. RESULTS: Weights of WD sows were lower prior to pregnancy (P = .04), however their weight gain over pregnancy did not differ from the CD group (P = .98). The WD sows had less total adipose tissue (TAT) at MR scanning (P = .04), while hepatic fat content was significantly elevated (P = .04). When controlling for litter size, WD fetuses had larger livers (P = .02), smaller brains (P = .01), and increased total adipose tissue volume (P = .01) when normalized by fetal volume. The WD fetuses also had increased hepatic fat fractions compared to CD fetal livers (P < .001). CONCLUSION: Maternal Western Diet consumption prior to and during pregnancy induces differences in maternal liver fat content, fetal liver volume and liver fat storage, as well as changes in fetal adipose tissue deposition that can be measured in utero using MRI.

Comparison of modified two-point dixon and chemical shift encoded MRI water-fat separation methods for fetal fat quantification.

BACKGROUND: Fetal fat is indicative of the energy balance within the fetus, which may be disrupted in pregnancy complications such as fetal growth restriction, macrosomia, and gestational diabetes. Water-fat separated MRI is a technique sensitive to tissue lipid content, measured as fat fraction (FF), and can be used to accurately measure fat volumes. Modified two-point Dixon and chemical shift encoded MRI (CSE-MRI) are water-fat separated MRI techniques that could be applied to imaging of fetal fat. Modified two-point Dixon has biases present that are corrected in CSE-MRI which may contribute to differences in the fat measurements. PURPOSE: To compare the measurement of fetal fat volume and FF by modified two-point Dixon and CSE-MRI. STUDY TYPE: Cross-sectional study for comparison of two MRI pulse sequences. POPULATION: Twenty-one pregnant women with singleton pregnancies. FIELD STRENGTH/SEQUENCE: 1.5T, modified two-point Dixon and CSE-MRI. ASSESSMENT: Manual segmentation of total fetal fat volume and mean FF from modified 2-point Dixon and CSE-MRI FF images. STATISTICAL TESTS: Reliability was assessed by calculating the intraclass correlation coefficient (ICC). Agreement was assessed using a one-sample t-test on the fat measurements difference values (modified two-point Dixon - CSE-MRI). The difference scores were tested against a value of 0, which would indicate that the measurements were identical. RESULTS: The fat volume and FF measured by modified two-point Dixon and CSE-MRI had excellent reliability, demonstrated by ICCs of 0.93 (P < 0.001) and 0.90 (P < 0.001), respectively. They were not in agreement, with CSE-MRI giving mean fat volumes 180 mL greater and mean FF 3.0% smaller than modified two-point Dixon. DATA CONCLUSION: The reliability between modified two-point Dixon and CSE-MRI indicates that either technique can be used to compare fetal fat measurements in different participants, but they are not in agreement possibly due to uncorrected biases in modified two-point Dixon. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018.