Empagliflozin Treatment Attenuates Hepatic Steatosis by Promoting White Adipose Expansion in Obese TallyHo Mice.

Sodium-glucose co-transporters (SGLTs) serve to reabsorb glucose in the kidney. Recently, these transporters, mainly SGLT2, have emerged as new therapeutic targets for patients with diabetes and kidney disease; by inhibiting glucose reabsorption, they promote glycosuria, weight loss, and improve glucose tolerance. They have also been linked to cardiac protection and mitigation of liver injury. However, to date, the mechanism(s) by which SGLT2 inhibition promotes systemic improvements is not fully appreciated. Using an obese TallyHo mouse model which recapitulates the human condition of diabetes and nonalcoholic fatty liver disease (NAFLD), we sought to determine how modulation of renal glucose handling impacts liver structure and function. Apart from an attenuation of hyperglycemia, Empagliflozin was found to decrease circulating triglycerides and lipid accumulation in the liver in male TallyHo mice. This correlated with lowered hepatic cholesterol esters. Using in vivo MRI analysis, we further determined that the reduction in hepatic steatosis in male TallyHo mice was associated with an increase in nuchal white fat indicative of "healthy adipose expansion". Notably, this whitening of the adipose came at the expense of brown adipose tissue. Collectively, these data indicate that the modulation of renal glucose handling has systemic effects and may be useful as a treatment option for NAFLD and steatohepatitis.

Tracing the destiny of mesenchymal stem cells from embryo to adult bone marrow and white adipose tissue via Pdgfrα expression.

Mesenchymal stem cells (MSCs) are somatic stem cells that can be derived from adult bone marrow (BM) and white adipose tissue (WAT), and that display multipotency and self-renewal capacity. Although MSCs are essential for tissue formation and have already been used in clinical therapy, the origins and markers of these cells remain unknown. In this study, we first investigated the developmental process of MSCs in mouse embryos using the gene encoding platelet-derived growth factor receptor α (Pdgfra) as a marker. We then traced cells expressing Pdgfra and other genes (brachyury, Sox1 and Pmx1) in various mutant mouse embryos until the adult stage. This tracing of MSC origins and destinies indicates that embryonic MSCs emerge in waves and that almost all adult BM MSCs and WAT MSCs originate from mesoderm and embryonic Pdgfrα-positive cells. Furthermore, we demonstrate that adult Pdgfrα-positive cells are involved in some pathological conditions.

Fasting and refeeding cycles alter subcutaneous white depot growth dynamics and the morphology of brown adipose tissue in female rats.

Intermittent food restriction (IFR) is used mainly for weight loss; however, its effects on adipose tissue are not known when alternating with an obesogenic diet. To demonstrate its effects on morphological dynamics of fat deposits, female Wistar rats were distributed into groups: standard control (ST-C), with commercial diet; DIO control (DIO-C), with a diet that induces obesity (DIO) during the first and last 15 d, replaced by a standard diet for thirty intermediate days; standard restricted (ST-R), with standard diet during the first and last 15 d, with six cycles of IFR at 50 % of ST-C; and DIO restricted (DIO-R), in DIO during the first and last 15 d, with six cycles of IFR at 50 % of DIO-C. At 105 d of life, white adipose tissue (WAT) and brown adipose tissue (BAT) deposits were collected, weighed and histology performed. The DIO-R group showed higher total food intake (DIO-R 10 768·0 (SEM 357·52) kJ/g v. DIO-C 8868·6 (SEM 249·25) kJ/g, P < 0·0001), energy efficiency during RAI (DIO-R 2·26 (SEM 0·05) g/kJ v. DIO-C 0·70 (SEM 0·03) g/kJ, P < 0·0001) and WAT (DIO-R 5·65 (SEM 0·30) g/100 g v. DIO-C 4·56 (SEM 0·30) g/100 g) than their respective control. Furthermore, IFR groups presented hypertrophy of WAT and BAT, as well as fibrosis in BAT. Thus, IFR can establish prospective resistance to weight loss by favouring changes in adipose tissue morphology, increased energy intake and efficiency. Finally, the DIO diet before and after IFR aggravates the damages caused by the restriction.

Enoyl coenzyme A hydratase 1 combats obesity and related metabolic disorders by promoting adipose tissue browning.

Browning of white adipose tissue (WAT) has been recognized as an important strategy for the treatment of obesity, insulin resistance, and diabetes. Enoyl coenzyme A hydratase 1 (ECH1) is a widely known enzyme involved in lipid metabolism. However, whether and how ECH1 is implicated in browning of WAT remain obscure. Adeno-associated, virus-mediated genetic engineering of ECH1 in adipose tissue was used in investigations in mouse models of obesity induced by a high-fat diet (HFD) or browning induced by cold exposure. Metabolic parameters showed that ECH1 overexpression decreased weight gain and improved insulin sensitivity and lipid profile after 8 wk of an HFD. Further work revealed that these changes were associated with enhanced energy expenditure and increased appearance of brown-like adipocytes in inguinal WAT, as verified by a remarkable increase in uncoupling protein 1 and thermogenic gene expression. In vitro, ECH1 induced brown fat-related gene expression in adipocytes differentiated from primary stromal vascular fractions, whereas knockdown of ECH1 reversed this effect. Mechanistically, ECH1 regulated the thermogenic program by inhibiting mammalian target of rapamycin signaling, which may partially explain the potential mechanism for ECH1 regulating adipose browning. In summary, ECH1 may participate in the pathology of obesity by regulating browning of WAT, which probably provides us with a new therapeutic strategy for combating obesity.

Schwann cell-specific Pten inactivation reveals essential role of the sympathetic nervous system activity in adipose tissue development.

There is increasing evidence that the sympathetic nervous system (SNS) plays an important role in adipose tissue development. However, the underlying molecular mechanism(s) associated with this remains unclear. SNS innervation of white adipose tissue (WAT) is believed to be necessary and sufficient to elicit WAT lipolysis. In this current study, mice with Schwann cell (SC)-specific inactivation of phosphatase and tensin homolog (Pten) displayed enlarged inguinal white adipose tissue (iWAT). This serendipitous observation implicates the role of SCs in mediating SNS activity associated with mouse adipose tissue development. Mice with SC-specific Pten inactivation displayed enlarged iWAT. Interestingly, the SNS activity in iWAT of SC-specific Pten-deficient mice was reduced as demonstrated by decreased tyrosine hydroxylase (TH) expression level and neurotransmitters, such as norepinephrine (NE) and histamine (H). The lipolysis related protein, phosphorylated hormone sensitive lipase (pHSL), was also decreased. As expected, AKT-associated signaling pathway was hyperactivated and hypothesized to induce enlarged iWAT in SC-specific Pten-deficient mice. Moreover, preliminary experiments using AKT inhibitor AZD5363 treatment ameliorated the enlarged iWAT condition in SC-specific Pten-deficient mice. Taken together, SCs play an essential role in the regulation of SNS activity in iWAT development via the AKT signaling pathway. This novel role of SCs in SNS function allows for better understanding into the genetic mechanisms of peripheral neuropathy associated obesity.

Deficiency of C1q/TNF-related protein 3 (CTRP3) decreases adipose tissue weight in diet-induced obesity mice.

Adipokines are important regulators of lipid and glucose metabolism. A family of adiponectin paralogs is known as C1q and tumor necrosis factor (TNF)-related proteins (CTRPs). One line of Ctrp3-deficient mice shows reduced liver size in response to obesity. We generated and characterized another line of Ctrp3 knockout (KO) mice to reveal novel physiological functions of CTRP3. Interestingly, high fat diet (HFD)-fed Ctrp3 KO mice displayed a decrease in the epididymal white adipose tissue (WAT) weight to total body weight ratio. Histologically, adipocyte size was significantly smaller in the epididymal WAT of HFD-fed Ctrp3 KO mice than wild-type (WT) controls. The expression of several genes involved in lipogenesis, lipolysis and adipogenesis in the epididymal WAT of Ctrp3 KO mice fed a HFD was decreased. The present findings provide new insight into the role of CTRP3 as adipokine in the regulation of adipose tissue in obesity.

The regulatory protein SnoN antagonizes activin/Smad2 protein signaling and thereby promotes adipocyte differentiation and obesity in mice.

Ski-related oncogene SnoN (SnoN or SKIL) regulates multiple signaling pathways in a tissue- and developmental stage-dependent manner and has broad functions in embryonic angiogenesis, mammary gland alveologenesis, cancer, and aging. Here, we report that SnoN also plays a critical role in white adipose tissue (WAT) development by regulating mesenchymal stem cell (MSC) self-renewal and differentiation. We found that SnoN promotes MSC differentiation in the adipocyte lineage by antagonizing activin A/Smad2, but not TGFß/Smad3 signaling. Mice lacking SnoN or expressing a mutant SnoN defective in binding to the Smads were protected from high-fat diet-induced obesity and insulin resistance, and MSCs lacking a functional SnoN exhibited defective differentiation. We further demonstrated that activin, via Smad2, appears to be the major regulator of WAT development in vivo We also noted that activin A is abundantly expressed in WAT and adipocytes through an autocrine mechanism and promotes MSC self-renewal and inhibits adipogenic differentiation by inducing expression of the gene encoding the homeobox transcription factor Nanog. Of note, SnoN repressed activin/Smad2 signaling and activin A expression, enabling expression of adipocyte-specific transcription factors and promoting adipogenic differentiation. In conclusion, our study has revealed that SnoN plays an important in vivo role in adipocyte differentiation and WAT development in vivo by decreasing activity in the activin/Smad2 signaling pathway.

Transcriptomic evidence that cortisol alters perinatal epicardial adipose tissue maturation.

Cortisol administration during late gestation in ewes, modeling maternal stress, resulted in transcriptomic changes suggesting altered maturation and metabolic changes to the offspring heart. This study investigates the effects of cortisol on epicardial adipose tissue (EAT), a visceral fat pad associated with adverse cardiovascular conditions in adults. Pregnant ewes were treated with either 1 mg·kg-1·day-1 cortisol from 115 days gestation to term and EAT collected from term fetuses (control: n = 8, maternal cortisol 1 mg·kg-1·day-1: n = 6). To compare the effects of cortisol to the normal maturation in EAT, we also modeled the normal changes in gene expression in EAT at the transition from in utero to postnatal life using the EAT from control fetuses and from two-week-old lambs (control: n = 7). Transcriptomic modeling was used to identify pathways altered by maternal cortisol overexposure. Transcriptomic modeling confirmed the brown fat phenotype of EAT at term and a transition toward white fat at 2 wk of age in EAT of control fetuses/lambs and highlighted a role of immune responses, including complement coagulation, and serotonin in this transition. Maternal cortisol (1 mg·kg-1·day-1) increased the lipid peroxidation product 4-hydroxynonenal in EAT of term fetuses but did not affect the number of activated macrophages or size of the lipid droplets in the depot; transcriptomics suggested an earlier metabolic maturation of EAT via, in part, increased immune responses.

Environmental temperature effects on adipose tissue growth in a hibernator.

Obligate hibernators express circannual patterns of body mass and hibernation, which persist under constant laboratory conditions. Brown adipose tissue (BAT) is important for thermogenesis during arousals from hibernation, whereas white adipose tissue (WAT) serves as energy storage and thermal insulation. The goal of this study was to investigate the effects of environmental temperature on BAT and WAT. We hypothesized that changes to environmental temperature would not influence the pattern of mass gain or BAT and WAT volume in the thirteen-lined ground squirrel (Ictidomys tridecemlineatus). To test this, we housed animals at thermoneutral 25°C (warm-housed) or 5°C (cold-housed), with the same photoperiod (12 h light:12 h dark) over an entire year. Throughout the year we measured the volume and water:fat ratio of WAT and BAT using magnetic resonance imaging (MRI). We found no evidence of torpor in the warm-housed animals, indicating that this species might not be an obligate hibernator, as previously assumed. Regardless of ambient temperature, BAT volume increased prior to winter, then decreased in late winter with no change in water:fat ratio. By contrast, both body mass and WAT volume of cold-housed animals declined throughout the winter and recovered after hibernation, but thermoneutral housing produced no circannual pattern in body mass, even though WAT volume declined in late winter. Cold exposure appears to be a primary regulator for WAT but BAT may exhibit an endogenous circannual rhythm in terms of depot volume.

Dietary vitamin A impacts DNA methylation patterns of adipogenesis-related genes in suckling rats.

We previously showed that vitamin A supplementation in early life impacts white adipose tissue (WAT) biology. We here studied the vitamin's effects on DNA methylation of genes crucial for WAT cell development, determination and metabolism. CpG promoter methylation and mRNA expression of Pparg, Zfp423, Pcna, and Rbp4 was compared in inguinal WAT of 21-day-old rats supplemented during the suckling period with vehicle (controls) or an emulsion of vitamin A as retinyl ester (RE) or ß-carotene (BC). The methylation profile of promoters was affected by vitamin A supplementation with pronounced differences between the RE and BC groups. In the RE group, hypermethylation of the Rbp4 (at multiple CpGs) and the Pparg2 (at a specific CpG) promoters and hypomethylation of the Pcna promoter (at multiple CpGs) was observed, together with inverse changes in gene expression levels. In the BC group, hypomethylation of the Rbp4 and hypermethylation of the Pcna promoter at distinct CpGs was observed, with no effects on gene expression. In both supplemention groups, hypomethylation and increased expression was found for Zfp423. Thus, modest vitamin A supplementation in early postnatal life impacts methylation marks in developing WAT. Differential epigenetic effects of RE and BC in early life may affect adipose tissue programming activity.

Serially Transplanted Nonpericytic CD146(-) Adipose Stromal/Stem Cells in Silk Bioscaffolds Regenerate Adipose Tissue In Vivo.

Progenitors derived from the stromal vascular fraction (SVF) of white adipose tissue (WAT) possess the ability to form clonal populations and differentiate along multiple lineage pathways. However, the literature continues to vacillate between defining adipocyte progenitors as "stromal" or "stem" cells. Recent studies have demonstrated that a nonpericytic subpopulation of adipose stromal cells, which possess the phenotype, CD45(-) /CD31(-) /CD146(-) /CD34(+) , are mesenchymal, and suggest this may be an endogenous progenitor subpopulation within adipose tissue. We hypothesized that an adipose progenitor could be sorted based on the expression of CD146, CD34, and/or CD29 and when implanted in vivo these cells can persist, proliferate, and regenerate a functional fat pad over serial transplants. SVF cells and culture expanded adipose stromal/stem cells (ASC) ubiquitously expressing the green fluorescent protein transgene (GFP-Tg) were fractionated by flow cytometry. Both freshly isolated SVF and culture expanded ASC were seeded in three-dimensional silk scaffolds, implanted subcutaneously in wild-type hosts, and serially transplanted. Six-week WAT constructs were removed and evaluated for the presence of GFP-Tg adipocytes and stem cells. Flow cytometry, quantitative polymerase chain reaction, and confocal microscopy demonstrated GFP-Tg cell persistence, proliferation, and expansion, respectively. Glycerol secretion and glucose uptake assays revealed GFP-Tg adipose was metabolically functional. Constructs seeded with GFP-Tg SVF cells or GFP-Tg ASC exhibited higher SVF yields from digested tissue, and higher construct weights, compared to nonseeded controls. Constructs derived from CD146(-) CD34(+) -enriched GFP-Tg ASC populations exhibited higher hemoglobin saturation, and higher frequency of GFP-Tg cells than unsorted or CD29(+) GFP-Tg ASC counterparts. These data demonstrated successful serial transplantation of nonpericytic adipose-derived progenitors that can reconstitute adipose tissue as a solid organ. These findings have the potential to provide new insights regarding the stem cell identity of adipose progenitor cells.

Role of developmental transcription factors in white, brown and beige adipose tissues.

In this review we discuss the role of developmental transcription factors in adipose tissue biology with a focus on how these developmental genes may contribute to regional variation in adipose tissue distribution and function. Regional, depot-specific, differences in lipid handling and signalling (lipolysis, lipid storage and adipokine/lipokine signalling) are important determinants of metabolic health. At a cellular level, preadipocytes removed from their original depot and cultured in vitro retain depot-specific functional properties, implying that these are intrinsic to the cells and not a function of their environment in situ. High throughput screening has identified a number of developmental transcription factors involved in embryological development, including members of the Homeobox and T-Box gene families, that are strongly differentially expressed between regional white adipose tissue depots and also between brown and white adipose tissue. However, the significance of depot-specific developmental signatures remains unclear. Developmental transcription factors determine body patterning during embryogenesis. The divergent developmental origins of regional adipose tissue depots may explain their differing functional characteristics. There is evidence from human genetics that developmental genes determine adipose tissue distribution: in GWAS studies a number of developmental genes have been identified as being correlated with anthropometric measures of adiposity and fat distribution. Additionally, compelling functional studies have recently implicated developmental genes in both white adipogenesis and the so-called 'browning' of white adipose tissue. Understanding the genetic and developmental pathways in adipose tissue may help uncover novel ways to intervene with the function of adipose tissue in order to promote health.

Adipose tissue plasticity from WAT to BAT and in between.

Adipose tissue plays an essential role in regulating energy balance through its metabolic, cellular and endocrine functions. Adipose tissue has been historically classified into anabolic white adipose tissue and catabolic brown adipose tissue. An explosion of new data, however, points to the remarkable heterogeneity among the cells types that can become adipocytes, as well as the inherent metabolic plasticity of mature cells. These data indicate that targeting cellular and metabolic plasticity of adipose tissue might provide new avenues for treatment of obesity-related diseases. This review will discuss the developmental origins of adipose tissue, the cellular complexity of adipose tissues, and the identification of progenitors that contribute to adipogenesis throughout development. We will touch upon the pathological remodeling of adipose tissue and discuss how our understanding of adipose tissue remodeling can uncover new therapeutic targets. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

Systemic regulation of adipose metabolism.

White adipose tissue serves as a critical energy storage depot and endocrine organ. Adipocytes are subject to numerous levels of regulation, including neuronal, endocrine and metabolic. While insulin is the classical endocrine regulator of lipid metabolism in adipose tissue, other important endocrine hormones also control adipose tissue physiology. In this review, we will focus on the contribution of the pituitary in the modulation of adipocyte function, through the direct release of growth hormone as well as via the regulation of the thyroid gland and release of thyroid hormone. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

Dietary protein intake affects expression of genes for lipid metabolism in porcine skeletal muscle in a genotype-dependent manner.

Skeletal muscle is a major site for the oxidation of fatty acids (FA) in mammals, including humans. Using a swine model, we tested the hypothesis that dietary protein intake regulates the expression of key genes for lipid metabolism in skeletal muscle. A total of ninety-six barrows (forty-eight pure-bred Bama mini-pigs (fatty genotype) and forty-eight Landrace pigs (lean genotype)) were fed from 5 weeks of age to market weight. Pigs of fatty or lean genotype were randomly assigned to one of two dietary treatments (low- or adequate-protein diet), with twenty-four individually fed pigs per treatment. Our data showed that dietary protein levels affected the expression of genes involved in the anabolism and catabolism of lipids in the longissimus dorsi and biceps femoris muscles in a genotype-dependent manner. Specifically, Bama mini-pigs had more intramuscular fat, SFA and MUFA, as well as elevated mRNA expression levels of lipogenic genes, compared with Landrace pigs. In contrast, Bama mini-pigs had lower mRNA expression levels of lipolytic genes than Landrace pigs fed an adequate-protein diet in the growing phase. These data are consistent with higher white-fat deposition in Bama mini-pigs than in Landrace pigs. In conclusion, adequate provision of dietary protein (amino acids) plays an important role in regulating the expression of key lipogenic genes, and the growth of white adipose tissue, in a genotype- and tissue-specific manner. These findings have important implications for developing novel dietary strategies in pig production.

Maternal supplementation of α-linolenic acid in normal and protein-restricted diets modulate lipid metabolism, adipose tissue growth and leptin levels in the suckling offspring.

BACKGROUND: Lipid quantity and quality have been shown to affect serum cholesterol, adipose and serum leptin levels during prenatal and postnatal dietary supplementation of adult rats. Maternal protein deficiency during pregnancy and lactation also affects polyunsaturated fatty acid (PUFA) levels in the offspring. The aim of the present study was to analyze the effect of α-linolenic acid (ALA; n-3) on n-3 PUFA accretion, lipid profile, leptin levels and adipose growth in normal and protein-restricted (deficient) dams and their suckling pups. METHODS: Garden cress oil rich in ALA (32%) was supplemented in the normal and protein-restricted (10%) diets and fed to rats for 8 weeks prior to gestation and during lactation. PUFA, cholesterol, triglycerides, leptin levels and retroperitoneal white adipose tissue weight (WAT) of the dams and the pups were analyzed at 3 weeks after delivery. RESULTS: The serum cholesterol levels were remarkably decreased (p < 0.01), and the n-3 PUFA levels were markedly increased (p < 0.05) in the pups of lactating normal and protein-deficient dams supplemented with ALA. Triglycerides were unaltered in the dams and the pups of different dietary groups. Serum leptin levels and relative WAT weights were lower (p < 0.01) in the pups of the ALA-supplemented normal and protein-deficient dams. CONCLUSION: Maternal supplementation of ALA in normal and protein-restricted diets modulates n-3 PUFA levels, cholesterol, leptin levels and also adipose growth in the suckling offspring.

Augmented expression and secretion of adipose-derived pigment epithelium-derived factor does not alter local angiogenesis or contribute to the development of systemic metabolic derangements.

Impaired coupling of adipose tissue expansion and vascularization is proposed to lead to adipocyte hypoxia and inflammation, which in turn contributes to systemic metabolic derangements. Pigment epithelium-derived factor (PEDF) is a powerful antiangiogenic factor that is secreted by adipocytes, elevated in obesity, and implicated in the development of insulin resistance. We explored the angiogenic and metabolic role of adipose-derived PEDF through in vivo studies of mice with overexpression of PEDF in adipocytes (PEDF-aP2). PEDF expression in white adipocytes and PEDF secretion from adipose tissue was increased in transgenic mice, but circulating levels of PEDF were not increased. Overexpression of PEDF did not alter vascularization, the partial pressure of O2, cellular hypoxia, or gene expression of inflammatory markers in adipose tissue. Energy expenditure and metabolic substrate utilization, body mass, and adiposity were not altered in PEDF-aP2 mice. Whole body glycemic control was normal as assessed by glucose and insulin tolerance tests, and adipocyte-specific glucose uptake was unaffected by PEDF overexpression. Adipocyte lipolysis was increased in PEDF-aP2 mice and associated with increased adipose triglyceride lipase and decreased perilipin 1 expression. Experiments conducted in mice rendered obese by high-fat feeding showed no differences between PEDF-aP2 and wild-type mice for body mass, adiposity, whole body energy expenditure, glucose tolerance, or adipose tissue oxygenation. Together, these data indicate that adipocyte-generated PEDF enhances lipolysis but question the role of PEDF as a major antiangiogenic or proinflammatory mediator in adipose tissue in vivo.

New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure.

Adipose tissue is central to the regulation of energy balance. Two functionally different types of fat are present in mammals: white adipose tissue, the primary site of triglyceride storage, and brown adipose tissue, which is specialized in energy expenditure and can counteract obesity. Factors that specify the developmental fate and function of white and brown adipose tissue remain poorly understood. Here we demonstrate that whereas some members of the family of bone morphogenetic proteins (BMPs) support white adipocyte differentiation, BMP7 singularly promotes differentiation of brown preadipocytes even in the absence of the normally required hormonal induction cocktail. BMP7 activates a full program of brown adipogenesis including induction of early regulators of brown fat fate PRDM16 (PR-domain-containing 16; ref. 4) and PGC-1alpha (peroxisome proliferator-activated receptor-gamma (PPARgamma) coactivator-1alpha; ref. 5), increased expression of the brown-fat-defining marker uncoupling protein 1 (UCP1) and adipogenic transcription factors PPARgamma and CCAAT/enhancer-binding proteins (C/EBPs), and induction of mitochondrial biogenesis via p38 mitogen-activated protein (MAP) kinase-(also known as Mapk14) and PGC-1-dependent pathways. Moreover, BMP7 triggers commitment of mesenchymal progenitor cells to a brown adipocyte lineage, and implantation of these cells into nude mice results in development of adipose tissue containing mostly brown adipocytes. Bmp7 knockout embryos show a marked paucity of brown fat and an almost complete absence of UCP1. Adenoviral-mediated expression of BMP7 in mice results in a significant increase in brown, but not white, fat mass and leads to an increase in energy expenditure and a reduction in weight gain. These data reveal an important role of BMP7 in promoting brown adipocyte differentiation and thermogenesis in vivo and in vitro, and provide a potential new therapeutic approach for the treatment of obesity.

Effect of two Spanish breeds and diet on beef quality including consumer preferences.

BACKGROUND: Farmers in dry mountain areas are changing their management strategies to improve livestock farming efficiency, by using different forages or different breeds. The effect of breed (Parda de Montaña vs. Pirenaica) and finishing diet (grazing on meadows vs. a total mixed ration (50% alfalfa, 40% maize grain, 10% straw)) on carcass characteristics and meat quality of steers was studied. RESULTS: Parda de Montaña had a greater (P < 0.01) amount of intramuscular fat than Pirenaica. The finishing diet did not influence carcass fat color, but fatty acid composition was slightly affected. Finishing steers on a total mixed ration increased the percentage of fat of the 10th rib (P < 0.001). Supplementation with concentrates increased the diet energy concentration and also increased the dressing percentage. CONCLUSIONS: Both breeds had similar carcass characteristics. Consumers preferred beef from the Pirenaica breed because of its greater tenderness. Consumers did not differentiate between beef from animals fed different finishing diets. However, consumers who like meat very much preferred meat aged in a cooler at 4 °C for 15 days rather than 8 days.

Developmental androgen excess programs sympathetic tone and adipose tissue dysfunction and predisposes to a cardiometabolic syndrome in female mice.

Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension.