Adipose Tissue Growth Research Articles

АНАЛІЗ ЯКІСНОГО СКЛАДУ МАТРИКСНИХ МЕТАЛОПРОТЕЇНАЗ У ПАТОГЕНЕЗІ ОЖИРІННЯ, ЩО ІНДУКОВАНЕ ВИСОКОКАЛОРІЙНОЮ ДІЄТОЮ У ЩУРІВ

The problem of obesity in modern life is becoming more actual and is a serious social risk for human life. This problem is common despite social and professional affiliation, location, age and gender. Obesity is associated with an increase growth of adipose tissue. Today obesity isn't studied only as an excessive accumulation of fat in the body, but as a chronic multivariate disease associated with a number of serious metabolic, oncological, cardiological and other complications. Although a lot of research studies regulation and intracellular processes of adipogenesis, however the information about molecular mechanisms of remodeling of the extracellular matrix during an increase fat mass is limited. Matrix metalloproteinases (MMPs) can increase the plasticity of the matrix, thereby providing adipose tissue remodeling and / or adipocyte hypertrophy, play an additional role in the growth of adipose tissue associated with obesity, supporting the differentiation of adipose tissue progenitor cells. Our research is aimed at characterization of enzymatic activitiesof MMPs in adipose tissue of the rats with obesity. We found that active enzymes with a molecular weight > 100 kDa were found in the adipose tissue of rats for the development of obesity, which may result from the formation of homodimers in these pathological conditions.Also activities of the MMP-2, -9 increase during obesity. Future studies of enzymatic activity of MMPs of rat's adipocytes tissues will improve understanding the biochemical processes under the conditions of this pathology and development of new approaches to diagnosis and treatment of obesity principles.

Sequence analyses of insulin-like growth factor 1 gene in Nigerian indigenous and arbor acre chickens

Alpha % Indigenous chicken % Gene % Sequence KR nema The chicken Insulin-like growth factor 1 (IGF1) is a candidate gene for growth, body composition and metabolism, skeletal characteristics and growth of adipose tissue and fat deposition in chickens. It is mapped to 165.95 cM on chromosome 1 and composed of four exons and three introns, spanning more than 50 kb. Genomic DNA was extracted from blood samples collected from the experimental birds using Qiagen DNA extraction kits. Polymersae chain reaction (PCR) was carried out using established primers. The PCR amplicon involving 5?untranslated region were sequenced. The sequences were analysed to identify polymorphisms, their genetic diversities and evolutionary relationships among three strains of Nigerian indigenous chickens [Frizzle Feathered (7), Normal Feathered (19) and Naked Neck (19), and the Arbor Acre broiler chicken (17)]. Nucleotide sequences generated were edited and aligned using Codon Code Aligner. Diversity analysis was done using DnaSp while MEGA6 software was used to plot phylogenetic tree using maximum likelihood method. A total of nineteen single nucleotide polymorphisms (SNPs) were detected from 560 bp portions of the 5?UTR among the four chicken populations studied with none detected in the Frizzle feathered chicken. The Naked neck chicken had the highest number of SNP?s (13), haplotypes (6), haplotype diversity (0.778), nucleotide diversity (0.00487), average number of nucleotide differences (2.725), highest number of polymorphic (segregating) sites (13), parsimony informative site (5) and singleton variable site (8). The Naked neck chicken therefore had the highest rate of mutation and degree of allelic variation compared to other chicken strains used in this study. The phylogenetic tree showed that small genetic differentiation exists among the chicken populations studied. Some of the SNPs are newly discovered; hence, association between these alleles and productive traits in Nigerian native chickens is desirable in future studies.

Sprouty1 regulates gonadal white adipose tissue growth through a PDGFRα/β-Akt pathway

ABSTRACT Expansion of visceral white adipose tissue (vWAT) occurs in response to nutrient excess, and is a risk factor for metabolic disease. SPRY1, a feedback inhibitor of receptor tyrosine kinase (RTK) signaling, is expressed in PDGFRa+ adipocyte progenitor cells (APC) in vivo. Global deficiency of Spry1 in mice results in disproportionate postnatal growth of gonadal WAT (gWAT), while iWAT and BAT were similar in size between Spry1KO and WT mice. Spry1 deficiency increased the number of PDGFRa+ stromal vascular fraction (SVF) cells in gWAT and showed increased proliferation and fibrosis. Spry1KO gWAT had increased collagen deposition and elevated expression of markers of inflammation. In vitro, SPRY1 was transiently down regulated during early adipocyte differentiation of SVF cells, with levels increasing at later stages of differentiation. SPRY1 deficiency enhances PDGF-AA and PDGF-BB induced proliferation of SVF cells. Increased proliferation of SVF from Spry1KO gWAT accompanies an increase in AKT activation. PDGF-AA stimulated a transient down regulation of SPRY1 in wild type SVF, whereas PDGF-BB stimulated a sustained down regulation of SPRY1 in wild type SVF. Collectively, our data suggest that SPRY1 is critical for regulating postnatal growth of gWAT by restraining APC proliferation and differentiation in part by regulation of PDGFRa/b-AKT signaling.

Potential mechanisms underlying the ameliorative effect of Lactobacillus paracasei FZU103 on the lipid metabolism in hyperlipidemic mice fed a high-fat diet

Lactobacillus paracasei FZU103, a probiotic previously isolated from the traditional brewing process of Hongqu rice wine, may have the beneficial effect of improving the disorder of lipid metabolism. This study aimed to determine the beneficial effects of L. paracasei FZU103 on improving hepatic lipid accumulation associated with hyperlipidemia. Results indicated that L. paracasei FZU103 intervention significantly inhibited the abnormal growth of body weight and epididymal white adipose tissue (eWAT), prevented the hypertrophy of epididymal adipocytes, ameliorated the biochemical parameters of serum and liver related to lipid metabolism in HFD-fed mice. Histological analysis also showed that the excessive accumulation oflipid dropletsin the livers induced by HFD-feeding was greatly alleviated by L. paracasei FZU103 intervention. In addition, L. paracasei FZU103 also promoted the excretion of bile acids (BAs) through feces. Metagenomic analysis revealed that oral supplementation with L. paracasei FZU103 significantly increased the relative abundance of Ruminococcus, Alistipes, Pseudoflavonifractor and Helicobacter, but decreased the levels of Blautia, Staphylococcos and Tannerella in HFD-fed mice. The relationships between lipid metabolic parameters and intestinal microbial phylotypes were also revealed by correlation heatmap and network. Furthermore, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS)-based liver metabolomics demonstrated that L. paracasei FZU103 had a significant regulatory effect on the metabolic pathways of glycerophospholipid metabolism, fatty acid degradation, fatty acid elongation, unsaturated fatty acids biosynthesis, riboflavin metabolism, glycerolipid metabolism, primary bile acid biosynthesis, arachidonic acid metabolism, etc. Additionally, L. paracasei FZU103 intervention regulated expression of hepatic genes involved in lipid metabolism and bile acid homeostasis, and promoted fecal excretion of intestinal BAs. These findings present new evidence supporting that L. paracasei FZU103 has the potential to improve lipid metabolism, and could be used as a potential functional food for the prevention of hyperlipidemia.

Adipose tissue growth and development: the modulating role of ambient temperature.

Adipose tissue is usually laid down in small amounts in the foetus and is characterised as possessing small amounts of the brown adipose tissue-specific mitochondrial uncoupling protein (UCP)1. In adults, a primary factor determining the abundance and function of UCP1 is ambient temperature. Cold exposure causes activation and the rapid generation of heat through the free flow of protons across the mitochondria with no requirement to convert ADP to ATP. In rodents, housing at an ambient temperature below thermoneutrality promotes the appearance of beige like adipocytes. These arise as discrete regions of UCP1 containing cells in white fat depots. There is increasing evidence to show that to gain credible translational results on brown and beige fat function in rodent models that they should be housed at thermoneutrality. This not only reflects the type of environment in which humans spend a majority of their time, but is in accord with the rise of global temperature caused by industrialisation and the uncontrolled burning of fossil fuels. There is now good evidence in adult humans, that stimulating brown fat can improve glucose homeostasis which can be achieved either by nutritional or pharmacological interventions. The challenge, therefore, is to establish credible developmental models in animals maintained at thermoneutrality which will elucidate the true impact of nutrition. The primary focus should fall specifically on the components of breast milk and how these modulate long term effects on brown or beige fat development and function.

Screening and Identification of Differentially Expressed and Adipose Growth-Related Protein-Coding Genes During the Deposition of Perirenal Adipose Tissue in Rabbits.

BackgroundRabbit is a good model for genetic and medical studies in other livestock species. The rabbit shows low adipose tissue deposition, and the phenomena indicates that there is some specificity of adipose deposition during the rabbit growth. However, little is known about genes that regulate the growth of adipose tissue in rabbits.Materials and MethodsDeep RNA-seq and comprehensive bioinformatics analyses were used to characterize the genes of rabbit visceral adipose tissue (VAT) at 35, 85 and 120 days after birth. Differentially expressed genes (DEGs) were identified at the three growth stages by DESeq. To explore the function of the candidate genes, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Six DEGs were randomly selected, and their expression profiles were validated by q-PCR.ResultsA total of 20,303 known transcripts and 99,199 new transcripts from 8 RNA sequencing libraries were identified, and 34 differentially expressed genes (DEGs) were screened. GO enrichment and KEGG pathway analyses revealed that the DEGs were mainly involved in lipid metabolism regulation including acylglycerol metabolic process and mobilization, and decomposition of lipids to generate ATP in adipocytes and fatty acid metabolism, included LOC100342322 and LOC100342572. In addition, 133 protein-coding genes that play a role in adipose growth and development were screened, including acyl-CoA synthetase long-chain family member 5 (ACSL5) and fatty acid-binding protein 2 (FABP2). The validation results of six DEGs by q-PCR showed similar trends with the results of RNA-seq.ConclusionIn summary, this study provides the first report of the coding genes profiles of rabbit adipose tissue during different growth stages. These data allow for the identification of candidate genes for subsequent studies on rabbit genetics and regulation of adipose cells, and provide an animal model for studying obesity in humans.

Both proliferation and lipogenesis of brown adipocytes contribute to postnatal brown adipose tissue growth in mice

Brown adipose tissue (BAT) is the primary non-shivering thermogenesis organ in mammals, which plays essential roles in maintaining the body temperature of infants. Although the development of BAT during embryogenesis has been well addressed in rodents, how BAT grows after birth remains unknown. Using mouse interscapular BAT (iBAT) as an example, we studied the cellular and molecular mechanisms that regulate postnatal BAT growth. By analyzing the developmental dynamics of brown adipocytes (BAs), we found that BAs size enlargement partially accounts for iBAT growth. By investigating the BAs cell cycle activities, we confirmed the presence of proliferative BAs in the neonatal mice. Two weeks after birth, most of the BAs exit cell cycle, and the further expansion of the BAT was mainly due to lipogenesis-mediated BAs volume increase. Microscopy and fluorescence-activated cell sorting analyses suggest that most BAs are mononuclear and diploid. Based on the developmental dynamics of brown adipocytes, we propose that the murine iBAT has two different growth phases between birth and weaning: increase of BAs size and number in the first two weeks, and BAs size enlargement thereafter. In summary, our data demonstrate that both lipogenesis and proliferation of BAs contribute to postnatal iBAT growth in mice.

Correction of Structural Changes in Thymus by <i>Gentiana algida</i> Pall Extract at Experimental Azathioprine Immunosuppression

The purpose of the studyis to evaluate the effect ofGentiana algidaPall dry extract on microanatomy of CBA mice thymus at azathioprine immunosuppression.Material and Methods. Experiments were carried out on CBA male mice. Immune deficiency was modeled by intragastrical administration of azathioprine in the dose 50 mg/kg once a day for 5 days. TheG.algidadry extract in the dose 50 mg/kg was administered to animals for 15 days against azathioprine. Morphological studies of the thymus were carried out on day 21 after the azathioprine administration. The area of the thymic lobule, the cortex and the medulla; the width of the cortex; the thickness and length of the medulla; the thickness of the capsule; the density of cells in the subcapsular zone and the deep layers of the cortex were measured using the Axio Vision SE64 Rel.4.8.3 image analysis program. The cellular composition was determined in the subcapsular and central zone of the cortex.Results. TheG.algidaextract limited the development of involutive changes in the thymus caused by cytostatic azathioprine: the cortex area was 16% higher and medulla area 17% lower compared with the control group. The ratio of cortex and medulla in experimental group was 1.4 times higher than that in the control group. TheG.algidaextract increased verage density of cells by 30% in the subcapsular zone. The number of blasts and large lymphocytes increased on average by 2.0 times in the deep layers of the cortex, and in the subcapsular zone - by 4.3 and 2.4 times, respectively, compared with those in control group.Conclusions:G.algidaextract limited the development of pronounced involutive processes in the thymus at azathioprin immunosuppression (increased the mitotic activity of thymocytes, reduced the severity of destructive processes and prevented the growth of adipose tissue).

Genomic regions and signaling pathways associated with indicator traits for feed efficiency in juvenile Atlantic salmon (Salmo salar)

BackgroundOne objective of this study was to identify putative quantitative trait loci (QTL) that affect indicator phenotypes for growth, nitrogen, and carbon metabolism in muscle, liver, and adipose tissue, and for feed efficiency. Another objective was to perform an RNAseq analysis (184 fish from all families), to identify genes that are associated with carbon and nitrogen metabolism in the liver. The material consisted of a family experiment that was performed in freshwater and included 2281 individuals from 23 full-sib families. During the 12-day feed conversion test, families were randomly allocated to family tanks (50 fish per tank and 2 tanks per family) and fed a fishmeal-based diet labeled with the stable isotopes 15N and 13C at inclusion levels of 2 and 1%, respectively.ResultsUsing a linear mixed-model algorithm, a QTL for pre-smolt growth was identified on chromosome 9 and a QTL for carbon metabolism in the liver was identified on chromosome 12 that was closely related to feed conversion ratio on a tank level. For the indicators of feed efficiency traits that were derived from the stable isotope ratios (15N and 13C) of muscle tissue and growth, no convincing QTL was detected, which suggests that these traits are polygenic. The transcriptomic analysis showed that high carbon and nitrogen metabolism was associated with individuals that convert protein from the feed more efficiently, primarily due to higher expression of the proteasome, lipid, and carbon metabolic pathways in liver. In addition, we identified seven transcription factors that were associated with carbon and nitrogen metabolism and located in the identified QTL regions.ConclusionsAnalyses revealed one QTL associated with pre-smolt growth and one QTL for carbon metabolism in the liver. Both of these traits are associated with feed efficiency. However, more accurate mapping of the putative QTL will require a more diverse family material. In this experiment, fish that have a high carbon and nitrogen metabolism in the liver converted protein from the feed more efficiently, potentially because of a higher expression of the proteasome, lipid, and carbon metabolic pathways in liver. Within the QTL regions, we detected seven transcription factors that were associated with carbon and nitrogen metabolism.

Mechanisms underlying the metabolic actions of testosterone in humans: A narrative review.

The role of testosterone in improving sexual symptoms in men with hypogonadism is well known. However, recent studies indicate that testosterone plays an important role in several metabolic functions in males. Multiple PubMed searches were conducted with the use of the terms testosterone, insulin sensitivity, obesity, type 2 diabetes, anaemia, bone density, osteoporosis, fat mass, lean mass and body composition. This narrative review is focused on detailing the mechanisms that underlie the metabolic aspects of testosterone therapy in humans. Testosterone enhances insulin sensitivity in obese men with hypogonadism by decreasing fat mass, increasing lean mass, decreasing free fatty acids and suppressing inflammation. At a cellular level, testosterone increases the expression of insulin receptor β subunit, insulin receptor substrate-1, protein kinase B and glucose transporter type 4 in adipose tissue and adenosine 5'-monophosphate-activated protein kinase expression and activity in skeletal muscle. Observational studies show that long-term therapy with testosterone prevents progression from prediabetes to diabetes and improves HbA1c. Testosterone increases skeletal muscle satellite cell activator, fibroblast growth factor-2 and decreases expression of the muscle growth suppressors, myostatin and myogenic regulatory factor 4. Testosterone increases haematocrit by suppressing hepcidin and increasing expression of ferroportin along with that of transferrin receptor and plasma transferrin concentrations. Testosterone also increases serum osteocalcin concentrations, which may account for its anabolic actions on bone. In conclusion, testosterone exerts a series of potent metabolic effects, which include insulin sensitization, maintenance and growth of the skeletal muscle, suppression of adipose tissue growth and maintenance of erythropoiesis and haematocrit.

Regulation of Obesity by Antiangiogenic Herbal Medicines.

Obesity is the result of an energy imbalance caused by an increased ratio of caloric intake to energy expenditure. In conjunction with obesity, related metabolic disorders, such as dyslipidemia, atherosclerosis, and type 2 diabetes, have become global health problems. Obesity progression is thought to be associated with angiogenesis and extracellular matrix (ECM) remodeling. Angiogenesis occurs in growing adult adipose tissues, which are similar to neoplastic tissues. Adipose tissue is highly vascularized, and each adipocyte is nourished by an extensive capillary network. Adipocytes produce proangiogenic factors, such as vascular endothelial growth factor A and fibroblast growth factor 2, which promote neovascularization within the adipose tissue. Furthermore, matrix metalloproteinases (MMPs), including MMP-2 and MMP-9, play important roles in adipose tissue development and microvessel maturation by modifying the ECM. Thus, modulation of angiogenesis and MMP activity provides a promising therapeutic approach for controlling human obesity and its related disorders. Over the past decade, there has been a great increase in the use of alternative treatments, such as herbal remedies, for these diseases. This review will focus on the role of angiogenesis in adipose tissue growth and the regulation of obesity by antiangiogenic herbal medicines.

Rationale for the design of 3D-printable bioresorbable tissue-engineering chambers to promote the growth of adipose tissue

Tissue engineering chambers (TECs) bring great hope in regenerative medicine as they allow the growth of adipose tissue for soft tissue reconstruction. To date, a wide range of TEC prototypes are available with different conceptions and volumes. Here, we addressed the influence of TEC design on fat flap growth in vivo as well as the possibility of using bioresorbable polymers for optimum TEC conception. In rats, adipose tissue growth is quicker under perforated TEC printed in polylactic acid than non-perforated ones (growth difference 3 to 5 times greater within 90 days). Histological analysis reveals the presence of viable adipocytes under a moderate (less than 15% of the flap volume) fibrous capsule infiltrated with CD68+ inflammatory cells. CD31-positive vascular cells are more abundant at the peripheral zone than in the central part of the fat flap. Cells in the TEC exhibit a specific metabolic profile of functional adipocytes identified by 1H-NMR. Regardless of the percentage of TEC porosity, the presence of a flat base allowed the growth of a larger fat volume (p < 0.05) as evidenced by MRI images. In pigs, bioresorbable TEC in poly[1,4-dioxane-2,5-dione] (polyglycolic acid) PURASORB PGS allows fat flap growth up to 75 000 mm3 at day 90, (corresponding to more than a 140% volume increase) while at the same time the TEC is largely resorbed. No systemic inflammatory response was observed. Histologically, the expansion of adipose tissue resulted mainly from an increase in the number of adipocytes rather than cell hypertrophy. Adipose tissue is surrounded by perfused blood vessels and encased in a thin fibrous connective tissue containing patches of CD163+ inflammatory cells. Our large preclinical evaluation defined the appropriate design for 3D-printable bioresorbable TECs and thus opens perspectives for further clinical applications.

Monascus purpureus-fermented common buckwheat protects against dyslipidemia and non-alcoholic fatty liver disease through the regulation of liver metabolome and intestinal microbiome

Monascus-fermented rice has been used to treat digestive disorder and promote blood circulation in China and other Asian countries for centuries. However, the effects and mechanisms of Monascus purpureus-fermented common buckwheat (HQ) on non-alcoholic fatty liver disease (NAFLD) and dyslipidemia are unclear. Here, oral supplementation of HQ significantly inhibited the abnormal growth of body weight and epididymal white adipose tissue (eWAT), prevented the hypertrophy of epididymal adipocytes, ameliorated some biochemical parameters of serum and liver related to lipid metabolism in mice fed a high-fat and high-cholesterol diet (HFD). Histological analysis also showed that the excessive accumulation of lipid droplets in the livers induced by HFD-feeding was greatly alleviated by HQ supplementation. Metagenomic analysis revealed that HQ supplementation made significant structural changes in the intestinal microflora of mice fed with HFD. The Spearman's correlation analysis revealed that physiological index, serum and liver lipid profiles were positively correlated with Bacteroidales S24-7, Streptococcus, Allobaculum, and Clostridiales XIII, but negatively associated with Lactobacillus, Ruminococcaceae_NK4A214 group, Ruminiclostridium, and Alistipes. UPLC-QTOF/MS-based liver metabolomics demonstrated that HQ intervention had significant regulatory effects on the metabolic pathways of primary bile acid biosynthesis, pyrimidine metabolism, ether lipid metabolism, glutathione metabolism, glycine, serine and threonine metabolism, and amino sugar and nucleotide sugar metabolism, etc. Additionally, HQ intervention regulated the mRNA levels of hepatic genes involved in hepatic lipid metabolism and bile acid homeostasis. Collectively, these findings present new evidence supporting that HQ has the potential to ameliorate dyslipidemia and NAFLD via modulating the intestinal microbial populations and hepatic metabolite profile in hyperlipidemic mice induced by HFD.

White, brown, and bone marrow adipose tissue behavior in DHEA-induced PCOS mice

Introduction: To investigate the behavior of white, brown, and bone marrow adipose tissue (MAT) and the insulin resistance in a PCOS mice model. Methods Thirty-one female C57BL/6J mice were divided into four groups: two were treated with subcutaneous dehydroepiandrosterone (DHEA) implants and divided into normal and hypercaloric diet (HFD). Two were control and divided into normal and HFD. Presence of insulin resistance, growth, and adipocyte markers expression of white and brown adipose tissues and growth and inflammatory cytokines expression of bone marrow adipose tissue were evaluated. Results Hypercaloric diet groups presented higher total weight gain and huge growth in all fat sites, except bone marrow. They also demonstrated greater expression of adipocyte markers in sites of white adipose tissue. DHEA + HFD group showed more insulin intolerance than all other groups. DHEA shows to abrogate AdipoQ expression in all fatty tissues. Conclusions DHEA alone does not influence adipose tissue growth, but contributes to increased insulin resistance and influences the expression of adipokines. Proximal MAT showed different behavior from the other fat depot.

Common Gene Modules Identified for Chicken Adiposity by Network Construction and Comparison.

Excessive fat deposition can cause chicken health problem, and affect production efficiency by causing great economic losses to the industry. However, the molecular underpinnings of the complex adiposity trait remain elusive. In the current study, we constructed and compared the gene co-expression networks on four transcriptome profiling datasets, from two chicken lines under divergent selection for abdominal fat contents, in an attempt to dissect network compositions underlying adipose tissue growth and development. After functional enrichment analysis, nine network modules important to adipogenesis were discovered to be involved in lipid metabolism, PPAR and insulin signaling pathways, and contained hub genes related to adipogenesis, cell cycle, inflammation, and protein synthesis. Moreover, after additional functional annotation and network module comparisons, common sub-modules of similar functionality for chicken fat deposition were identified for different chicken lines, apart from modules specific to each chicken line. We further validated the lysosome pathway, and found TFEB and its downstream target genes showed similar expression patterns along with chicken preadipocyte differentiation. Our findings could provide novel insights into the genetic basis of complex adiposity traits, as well as human obesity and related metabolic diseases.

Microevolutionary Dynamics of Chicken Genomes under Divergent Selection for Adiposity.

SummaryDecades of artificial selection have significantly improved performance and efficiency of animal production systems. However, little is known about the microevolution of genomes due to intensive breeding. Using whole-genome sequencing, we document dynamic changes of chicken genomes under divergent selection on adiposity over 19 generations. Directional selection reduced within-line but increased between-line genomic differences. We observed that artificial selection tended to result in recruitment of preexisting variations of genes related to adipose tissue growth. In addition, novel mutations contributed to divergence of phenotypes under selection but contributed significantly less than preexisting genomic variants. Integration of 15 generations genome sequencing, genome-wide association study, and multi-omics data further identified that genes involved in signaling pathways important to adipogenesis, such as autophagy and lysosome (URI1, MBL2), neural system (CHAT), and endocrine (PCSK1) pathways, were under strong selection. Our study provides insights into the microevolutionary dynamics of domestic animal genomes under artificial selection.

MON-695 Multiple Recurrent Lipomatoses with Thiazolidinedione Therapy in Familial Partial Lipodystrophy, Dunnigan Variety (FPLD2)

Background: FPLD2, a rare autosomal dominant disorder due to heterozygous missense mutations in LMNA, is characterized by gradual loss of subcutaneous (sc) fat from the limbs starting during late childhood and predisposition to metabolic complications, such as diabetes, dyslipidemia and hepatic steatosis. Some patients, especially females, accumulate excess sc fat in the chin, neck, supraclavicular and perineal regions. We report disfiguring and disabling lipomatoses in unusual locations with thiazolidinedione therapy in two women with FPLD2. Clinical Cases: A 57-year-old white female with FPLD2, due to heterozygous p.R482Q LMNA mutation, developed recurrent large lipomatoses in the axillae at age 33 years, and later in the posterior neck (buffalo hump), mons pubis and above sacrum. She developed diabetes at age 30 and was started on pioglitazone 45 mg daily, which was switched to rosiglitazone 8 mg daily at age 43 years. Supra-sacral lipomatoses were approximately 40 cm X 20 cm bilaterally and continued to grow despite lipectomy and multiple liposuctions. Rosiglitazone was stopped at age 56 years, and she reported no further increase in the size of lipomatoses. Her other medications included colesevelam, atorvastatin, metformin, glimepiride, lisinopril, losartan, hydrochlorothiazide, aspirin, insulin and dulaglutide. Her 54-year-old younger sister with FPLD2 (heterozygous p.R482Q LMNA mutation) was treated with lisinopril, metoprolol, atorvastatin, liraglutide, and insulin glargine and aspart, but no history of taking thiazolidinediones, and she never developed any lipomatoses. Another 43-year-old white female with FPLD2, due to heterozygous p.S583L LMNA mutation, was noticed to have lipomatous deposits in the axillae, medial gluteal region, labia and perineal regions. She developed diabetes mellitus at age 36 years and took metformin for 6 years and pioglitazone 30 mg daily for one year before she noticed the lipomatoses. Her other medications included atorvastatin, aldactone and vitamin D3. Pioglitazone was stopped and after one year, she reported reduction in the size of lipomatoses. Conclusion: Thiazolidinediones are selective peroxisomal proliferator-activated receptor-γ agonists and induce weight gain by increasing fat mass, especially subcutaneous depots. Our cases suggest that thiazolidinediones can cause undesired growth of non-lipodystrophic adipose tissue in patients with FPLD2 and thus should be avoided.

Feeding Faba Beans (Vicia faba L.) Reduces Myocyte Metabolic Activity in Grass Carp (Ctenopharyngodon idellus).

In this study, we aimed to explore the effects of faba bean (Vicia faba L.) on the energy metabolism of grass carp (Ctenopharyngodon idellus). A total of 180 fish (∼2900 g) were randomly assigned to six tanks (2.5 × 2.5 × 1.2 m; 30 individuals per tank) and fed either faba bean (Vicia faba L.) or a commercial diet for 120 days (3% body weight, twice per day). The results showed that faba bean-fed grass carp (FBFG) had significantly lower growth and higher fat accumulation in the mesenteric adipose tissue and hepatopancreas than commercial diet-fed grass carp (CDFG). Compared with CDFG, FBFG exhibited no significant difference in proximate composition of the muscle; however, an obvious decrease in muscle fiber size and significantly higher hardness, chewiness, and gumminess were observed. Transcriptome results showed that a total of 197 genes were differentially regulated in the dorsal muscle. Down-regulated genes included four genes annotated with myocyte development and 12 transcripts annotated with components of myofibrils. In addition, the FBFG group exhibited significantly lower expression of genes associated with oxygen transport, the mitochondrial respiratory chain, and creatine metabolism, suggesting reduced energy availability in the muscle of the FBFG. Moreover, using western-blotting and enzyme assays, we found decreased protein levels in the mitochondrial electron transport respiratory chain and creatine metabolism activities, as well as increased expression of autophagy marker protein levels, in the muscle of FBFG. Overall, our results suggest that an abnormal energy distribution may exist in grass carps after feeding with faba bean, which is reflected by a mass of fat deposition in the adipose tissue and hepatopancreas and subdued metabolic activity in the muscle.

Real-ambient exposure to air pollution exaggerates excessive growth of adipose tissue modulated by Nrf2 signal

Air pollution was becoming a global threat to the public health, which was primarily mediated by PM2.5 induced cardiovascular diseases and pulmonary diseases. Recently, observational epidemiologic studies proposed the link between PM2.5 and obesity. Consistently, the link was also supported by limited animal researches. However, the potential mechanism mediating the harmful effects of PM2.5 was still elusive. In this study, we applied the “real-ambient exposure” system to conduct the experiments, which was closer to the status of ambient air pollution compared with the method of intratracheal instillation and concentrated air particles (CAPs) exposure system. Nuclear factor E2-related factor 2 (Nrf2) was previously reported to protect against inflammation and oxidative stress when exposed to PM2.5. Here, we reported that Nrf2−/− mice developed overgrowth of adipose tissue after “real-ambient exposure” to PM2.5, compared to filtered air (FA) group. Consistently, compared to FA group, adipocytes from subcutaneous (sWAT) and gonadal (gWAT) white adipose tissue of Nrf2−/− mice exhibited enlarged cell size in PM2.5 exposure group. Furthermore, the levels of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) in serum and liver of Nrf2−/− mice were also altered statistically in PM2.5 exposure group. Importantly, when the expression of lipogenic enzymes was analyzed, the levels of the related specific genes in adipose tissue and liver of Nrf2−/− mice were altered in PM2.5 exposure group. Interestingly, the key transcription factors modulating expression of lipogenic enzymes in liver of Nrf2−/− mice were also found altered in PM2.5 exposure group, such as peroxisome proliferator-activated receptor (PPARα, PPARγ). Taken together, our study mimicked the status of ambient air pollution, revealed new insights into the adverse effect of PM2.5 exposure, provided new link between air pollution and overgrowth of adipose tissue, and supported the vital role of Nrf2 in mediating the side effects of PM2.5.

Thyroid Deficiency Before Birth Alters the Adipose Transcriptome to Promote Overgrowth of White Adipose Tissue and Impair Thermogenic Capacity.

Background: Development of adipose tissue before birth is essential for energy storage and thermoregulation in the neonate and for cardiometabolic health in later life. Thyroid hormones are important regulators of growth and maturation in fetal tissues. Offspring hypothyroid in utero are poorly adapted to regulate body temperature at birth and are at risk of becoming obese and insulin resistant in childhood. The mechanisms by which thyroid hormones regulate the growth and development of adipose tissue in the fetus, however, are unclear. Methods: This study examined the structure, transcriptome, and protein expression of perirenal adipose tissue (PAT) in a fetal sheep model of thyroid hormone deficiency during late gestation. Proportions of unilocular (UL) (white) and multilocular (ML) (brown) adipocytes, and UL adipocyte size, were assessed by histological and stereological techniques. Changes to the adipose transcriptome were investigated by RNA sequencing and bioinformatic analysis, and proteins of interest were quantified by Western blotting. Results: Hypothyroidism in utero resulted in elevated plasma insulin and leptin concentrations and overgrowth of PAT in the fetus, specifically due to hyperplasia and hypertrophy of UL adipocytes with no change in ML adipocyte mass. RNA sequencing and genomic analyses showed that thyroid deficiency affected 34% of the genes identified in fetal adipose tissue. Enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathways were associated with adipogenic, metabolic, and thermoregulatory processes, insulin resistance, and a range of endocrine and adipocytokine signaling pathways. Adipose protein levels of signaling molecules, including phosphorylated S6-kinase (pS6K), glucose transporter isoform 4 (GLUT4), and peroxisome proliferator-activated receptor γ (PPARγ), were increased by fetal hypothyroidism. Fetal thyroid deficiency decreased uncoupling protein 1 (UCP1) protein and mRNA content, and UCP1 thermogenic capacity without any change in ML adipocyte mass. Conclusions: Growth and development of adipose tissue before birth is sensitive to thyroid hormone status in utero. Changes to the adipose transcriptome and phenotype observed in the hypothyroid fetus may have consequences for neonatal survival and the risk of obesity and metabolic dysfunction in later life.