Catch-up growth in juvenile rats, fat expansion, and dysregulation of visceral adipose tissue.

BACKGROUND: Accelerated catch-up growth following intrauterine restriction increases the risk of developing visceral adiposity and metabolic abnormalities. However, the underlying molecular mechanisms of such metabolic programming are still poorly understood. METHODS: A Wistar rat model of catch-up growth following intrauterine restriction was used. A gene expression array was performed in the retroperitoneal adipose tissue sampled at postnatal day (PD) 42. RESULTS: Five hundred and forty-six differentially expressed genes (DEGs) were identified (adjusted p value < 0.05). Gene ontology enrichment analysis identified pathways related to immune and lipid metabolic processes, brown fat cell differentiation, and regulation of PI3K. Ccl21, Npr3, Serpina3n, Pnpla3, Slc2a4, and Serpina12 were validated to be upregulated in catch-up pups (all p < 0.01) and related to several fat expansion and metabolic parameters, including body weight at PD42, postnatal body weight gain, white and brown adipose tissue mass, plasma triglycerides, and insulin resistance index (all p < 0.05). CONCLUSIONS: Genes related to immune and metabolic processes were upregulated in retroperitoneal adipose tissue following catch-up growth in juvenile rats and were found to be associated with fat expansion and metabolic parameters. Our results provide evidence for several dysregulated genes in white adipose tissue that could help develop novel strategies to prevent the metabolic abnormalities associated with catch-up growth. IMPACT: Catch-up growth presents several dysregulated genes in white adipose tissue related to metabolic abnormalities. Ccl21, Npr3, Serpina3n, Pnpla3, Slc2a4, and Serpina12 were validated to be upregulated in catch-up pups and related to visceral fat expansion and metabolic parameters. Profiling and validation of these dysregulated genes in visceral adipose tissue could help develop novel strategies to prevent the metabolic abnormalities associated with catch-up growth.

Visceral Fat Area by Abdominal Bioelectrical Impedance Analysis as a Risk of Obstructive Sleep Apnea.

This is the first study to evaluate directly visceral fat area (VFA) using a visceral fat (VF) meter by the abdominal bioelectrical impedance analysis (A-BIA) method in obstructive sleep apnea (OSA) patients diagnosed with polysomnography (PSG). The purpose of this study is to clarify (1) whether VFA measurement using a VF meter by the A-BIA method is possible even in a private clinic without burdening patients and staff and (2) how much VFA affects OSA compared to body mass index (BMI). Even without a computed tomography scan, which is the gold standard for VFA measurement, a VF meter could analyze patients by the A-BIA method and easily measure VFA. Therefore, it could be used safely even in a private sleep clinic, with very little burden on the patients and the medical staff. We investigated the association between OSA and VFA in 133 OSA patients. Multiple regression analysis revealed that VFA (ß = 0.28; P = 0.020) was a stronger coexisting factor for OSA than age, male gender, or BMI (ß = 0.26; P = 0.032) in all OSA patients. In the OSA patients with VF accumulation, only VFA was a significant component of OSA severity (ß = 0.36; P = 0.006). The A-BIA method instrument could become a useful device for the evaluation of VF accumulation in OSA patients in private sleep clinics. VF accumulation should be recognized as an important risk factor as well as a known risk factor for OSA.

Hypothalamic Renin-Angiotensin System and Lipid Metabolism: Effects of Virgin Olive Oil versus Butter in the Diet.

The brain renin-angiotensin system (RAS) has been recently involved in the homeostatic regulation of energy. Our goal was to analyse the influence of a diet rich in saturated fatty acids (butter) against one enriched in monounsaturated fatty acids (olive oil) on hypothalamic RAS, and their relationship with the metabolism of fatty acids. Increases in body weight and visceral fat, together with an increase in aminopeptidase A expression and reductions in AngII and AngIV were observed in the hypothalamus of animals fed with the butter diet. In this group, a marked reduction in the expression of genes related to lipid metabolism (LPL, CD36, and CPT-1) was observed in liver and muscle. No changes were found in terms of body weight, total visceral fat and the expression of hepatic genes related to fatty acid metabolism in the olive oil diet. The expressions of LPL and CD36 were reduced in the muscles, although the decrease was lower than in the butter diet. At the same time, the fasting levels of leptin were reduced, no changes were observed in the hypothalamic expression of aminopeptidase A and decreases were noted in the levels of AngII, AngIV and AngIII. These results support that the type of dietary fat is able to modify the hypothalamic profile of RAS and the body energy balance, related to changes in lipid metabolism.

Visceral adiposity index is a better predictor of type 2 diabetes than body mass index in Qatari population.

The prevalence of type 2 diabetes (T2D) has increased recently in Qatar. Body mass index (BMI) is a predictor of T2D in many populations. However, BMI is based on height and weight measurements and not on body adiposity. Therefore, the utility of BMI for predicting the risk of T2D has been questioned. Visceral adiposity appears to be a better predictor of T2D.This study aimed to assess the relative effectiveness of visceral adiposity index (VAI) and body adiposity index (BAI), in comparison with BMI, for T2D among Qatari adults.A random sample of 1103 adult Qatari nationals and long term residents over 20 years old were included in this study. This data were obtained from the Qatar Biobank (QBB). We performed a multivariate logistic regression to examine the association between VAI, BAI, BMI, and T2D, and computed z-scores for VAI, BAI and BMI.VAI z-scores showed the strongest association with the risk of T2D (OR, 1.44; 95% CI: 1.24-1.68) compared with the z-scores for BAI (OR, 1.15; 95% CI: 0.93-1.43) and BMI (OR, 1.33; 95% CI: 1.11-1.59). ROC curve analysis showed that VAI was a stronger predictor than BAI and BMI (P < .0001). Subgroup analysis indicated that the association was stronger between VAI and T2D in Qatari women than in men.VAI was a stronger and an independent predictor of T2D compared to BAI and BMI among the Qatari adult population. Therefore, VAI could be a useful tool for predicting the risk of T2D among Qatari adults.

Perirenal fat thickness as a predictor of postoperative complications after laparoscopic distal gastrectomy for gastric cancer.

BACKGROUND: Laparoscopic distal gastrectomy is used widely in surgery for gastric cancer. Excess visceral fat can limit the ability to dissect the suprapancreatic region, potentially increasing the risk of local complications, particularly pancreatic fistula. This study evaluated perirenal fat thickness as a surrogate for visceral fat to see whether this was related to complications after laparoscopic distal gastrectomy. METHODS: Perirenal fat thickness was measured dorsal to the left kidney as an indicator of visceral fat in patients with gastric cancer who underwent laparoscopic distal gastrectomy. Patients were divided into two groups: those with and those without complications. The relationship between perirenal fat thickness and postoperative complications was evaluated. RESULTS: The optimal cut-off value for predicting morbidity using adipose tissue thickness was 10·7 mm; a distance equal to or greater than this was considered a positive perirenal fat thickness sign (PTS). A positive PTS showed a significant correlation with visceral fat area. Multivariable analysis found that a positive PTS was an independent risk factor for complications (hazard ratio 4·42, 95 per cent c.i. 2·31 to 8·86; P < 0·001). CONCLUSION: Perirenal fat thickness as an indicator of visceral fat was an independent predictor of postoperative complications after laparoscopic distal gastrectomy for gastric cancer.

ANTECEDENTES: La gastrectomía distal laparoscópica se utiliza ampliamente en la cirugía del cáncer gástrico. El exceso de grasa visceral puede limitar la capacidad para disecar la región suprapancreática, aumentando potencialmente riesgo de complicaciones locales, especialmente de fistula pancreática. El propósito de este estudio fue evaluar el grosor de la grasa perirrenal como marcador subrogado de grasa visceral para determinar si se relacionaba con complicaciones tras gastrectomía distal laparoscópica. MÉTODOS: El grosor de la grasa perirrenal se midió a nivel dorsal del riñón izquierdo como indicador de grasa visceral en pacientes con cáncer gástrico sometidos a gastrectomía distal laparoscópica. Los pacientes fueron divididos en dos grupos: aquellos con y sin complicaciones. Se evaluó la relación entre grosor de la grasa perirrenal y las complicaciones postoperatorias. RESULTADOS: El punto de corte óptimo para predecir la morbilidad utilizando el grosor del tejido adiposo fue de 10,7 mm, por lo que una distancia igual o mayor a este nivel fue considerado como signo positivo de engrosamiento de la grasa perirrenal (peri-renal fat thickness sign, PTS). Un PTS positivo mostró una correlación significativa con el área de grasa visceral. Los análisis multivariables demostraban que un PTS positivo era un factor de riesgo independiente para complicaciones (razón de oportunidades, odds ratio 4,418; i.c. del 95% 2,307-8,855; P < 0,001). CONCLUSIÓN: El grosor de grasa perirrenal como indicador de la grasa visceral fue un predictor independiente de complicaciones postoperatorias tras una gastrectomía distal laparoscópica por cáncer gástrico.

Resolution of Metabolic syndrome with reduction of visceral adipose tissue in a 47 year old patient with Type 2 Diabetes Mellitus.

BACKGROUND AND AIMS: Metabolic syndrome (MetS), defined as a cluster of metabolic abnormalities including visceral adiposity, insulin resistance, hypertension, and dyslipidemia, now affects more than a third of adults in the United States highlighting the need for effective complementary approaches to current treatments. METHODS: We present a case report of a 47-year-old man with a history of MetS and poorly controlled Type 2 Diabetes Mellitus (T2D) who completed a 20Lighter program (20L) including a very low calorie diet (VLCD). At the time of enrollment his BMI was 32.7, HbA1c was 9.6%, and prescription medication history included lisinopril, lovastatin, and metformin, glimepiride, and combination sitagliptin/metformin. RESULTS: Fifteen weeks after beginning 20L (6 weeks after program completion) marked reduction of weight, visceral adipose tissue and normalization of HbA1C was seen, and all medications were withdrawn. CONCLUSIONS: While longer follow-up is required, this case report shows that a comprehensive program including a relatively short period of nutritionally complete VLCD, followed by gradual return to moderate dietary lifestyle is capable of producing clinically significant improvements in health and quality of life in individuals with MetS and poorly controlled T2D.

Developmental programming: Transcriptional regulation of visceral and subcutaneous adipose by prenatal bisphenol-A in female sheep.

BACKGROUND: Bisphenol-A (BPA) exposure is widespread and early life exposure is associated with metabolic syndrome. While visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are implicated in the development of metabolic syndrome, the adipose depot-specific effects of prenatal BPA treatment are poorly understood. OBJECTIVE: To determine the impact of prenatal BPA exposure on genome-wide gene expression of VAT and SAT depots. METHODS: RNA sequencing was performed on SAT and VAT from 21-month old control and prenatal BPA-treated female sheep. Gene expression and pathway differences between SAT and VAT depots with or without prenatal BPA-treatment and the effect of prenatal BPA treatment on each depot were tested. RESULTS: There were 179 differentially expressed genes (padjusted < 0.05, log2-fold change >2.5) between SAT and VAT. Development and immune response pathways were upregulated in SAT, while metabolic pathways were upregulated in VAT. These adipose depot-specific genes and pathways were consistent with prenatal BPA-treatment. In SAT, BPA-treatment resulted in differential expression of 108 genes (78% upregulated with BPA) and altered pathways (immune response downregulated, RNA processing upregulated). In contrast in VAT, BPA-treatment differentially expressed 4 genes and upregulated chromatin and RNA processing pathways. CONCLUSION: Prenatal BPA-treatment induces adult depot-specific alterations in RNA expression in inflammation, RNA processing, and chromatin pathways, reflecting the diverse roles of SAT and VAT in regulating lipid storage and insulin sensitivity. These adipose tissue transcriptional dysregulations may contribute to the metabolic disorders observed in prenatal BPA-treated female sheep.

Blood pressure response to treatment of obese vs non-obese adults with sleep apnea.

Many patients with obstructive sleep apnea (OSA), but not all, have a reduction in blood pressure (BP) with positive airway pressure (PAP) treatment. Our objective was to determine whether the BP response following PAP treatment is related to obesity. A total of 188 adults with OSA underwent 24-hour BP monitoring and 24-hour urinary norepinephrine collection at baseline. Obesity was assessed by waist circumference, body mass index, and abdominal visceral fat volume. Participants adherent to PAP treatment were reassessed after 4 months. Primary outcomes were 24-hour mean arterial pressure (MAP) and 24-hour urinary norepinephrine level. Obstructive sleep apnea participants had a significant reduction in 24-hour MAP following PAP treatment (-1.22 [95% CI: -2.38, -0.06] mm Hg; P = .039). No significant correlations were present with any of the 3 obesity measures for BP or urinary norepinephrine measures at baseline in all OSA participants or for changes in BP measures in participants adherent to PAP treatment. Changes in BP measures following treatment were not correlated with baseline or change in urinary norepinephrine. Similar results were obtained when BP or urinary norepinephrine measures were compared between participants dichotomized using the sex-specific median of each obesity measure. Greater reductions in urinary norepinephrine were correlated with higher waist circumference (rho = -0.21, P = .037), with a greater decrease from baseline in obese compared to non-obese participants (-6.26 [-8.82, -3.69] vs -2.14 [-4.63, 0.35] ng/mg creatinine; P = .027). The results indicate that the BP response to PAP treatment in adults with OSA is not related to obesity or urinary norepinephrine levels.

Dlk1 expression relates to visceral fat expansion and insulin resistance in male and female rats with postnatal catch-up growth.

BACKGROUND: Although prenatal and postnatal programming of metabolic diseases in adulthood is well established, the mechanisms underpinning metabolic programming are not. Dlk1, a key regulator of fetal development, inhibits adipocyte differentiation and restricts fetal growth. METHODS: Assess DLk1 expression in a Wistar rat model of catch-up growth following intrauterine restriction. Dams fed ad libitum delivered control pups (C) and dams on a 50% calorie-restricted diet delivered pups with low birth weight (R). Restricted offspring fed a standard rat chow showed catch-up growth (R/C) but those kept on a calorie-restricted diet did not (R/R). RESULTS: Decreased Dlk1 expression was observed in adipose tissue and skeletal muscle of R/C pups along with excessive visceral fat accumulation, decreased circulating adiponectin, increased triglycerides and HOMA-IR (from p < 0.05 to p < 0.0001). Moreover, in R/C pups the reduced Dlk1 expression in adipose tissue and skeletal muscle correlated with visceral fat (r = -0.820, p < 00001) and HOMA-IR (r = -0.745, p = 0.002). CONCLUSIONS: Decreased Dlk1 expression relates to visceral fat expansion and insulin resistance in a rat model of catch-up growth following prenatal growth restriction. Modulation of Dlk1 expression could be among the targets for the early prevention of fetal programming of adult metabolic disorders.

Higher High Density Lipoprotein 2 (HDL2) to Total HDL Cholesterol Ratio Is Associated with a Lower Risk for Incident Hypertension.

BACKGROUND: Recent studies have suggested that high density lipoprotein (HDL) cholesterol is inversely associated with the development of hypertension. We aimed to determine the association between different HDL cholesterol subclasses and risk of future hypertension. METHODS: A total of 270 Japanese Americans (130 men, 140 women) without hypertension between the ages of 34 to 75 years were enrolled. Blood pressure was measured with a mercury sphygmomanometer, and average blood pressure was calculated. Incident hypertension was determined 5 to 6 and 10 to 11 years after enrollment. HDL2, HDL3, and total HDL cholesterol were measured at baseline. RESULTS: During 10 years of follow-up, the cumulative incidence of hypertension was 28.1% (76/270). In univariate analysis, age, diabetes, waist circumference, systolic and diastolic blood pressure, fasting glucose, insulin resistance index, total and low density lipoprotein cholesterol, and visceral adipose tissue were significant predictors for incident hypertension. Among the HDL cholesterol subclass, HDL2 cholesterol was inversely associated with hypertension incidence, but both total and HDL3 cholesterol were not. In addition, HDL2/HDL cholesterol was inversely associated with future hypertension risk. In multivariate analysis, age (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26 to 2.31; P=0.001), systolic blood pressure (OR, 1.83; 95% CI, 1.31 to 2.56; P<0.001), and HDL2/HDL cholesterol (OR, 0.71; 95% CI, 0.52 to 0.98; P=0.035), were associated with future development of hypertension. CONCLUSION: A higher proportion of HDL2 cholesterol among total HDL cholesterol predicted a lower risk for incident hypertension. However, concentrations of total HDL, HDL2, and HDL3 cholesterol were not independent predictors of incident hypertension.

Simultaneous Intake of Euglena Gracilis and Vegetables Synergistically Exerts an Anti-Inflammatory Effect and Attenuates Visceral Fat Accumulation by Affecting Gut Microbiota in Mice.

We determined whether the benefits provided by the consumption of Euglena gracilis (Euglena), which is a unicellular photosynthesizing green alga and rich in insoluble dietary fiber paramylon, can be enhanced by the co-consumption of vegetables that are rich in soluble dietary fiber. Nine-week-old male C57BL/6J mice were divided into four groups: group 1 received normal diet, whereas groups 2, 3 and 4 received normal diet containing 0.3% paramylon, 1.0% Euglena, or 1.0% Euglena plus 0.3% vegetables (barley leaf, kale and ashitaba), respectively. Mice were fed ad libitum until 18 weeks of age. Euglena intake significantly decreased serum markers of inflammation and co-consumption of vegetables enhanced this reduction. Notably, we observed an increase in the fraction of beneficial bacteria producing short-chain fatty acids, a reduction in harmful bacteria that cause inflammation and an increase in short-chain fatty acid production. Visceral fat accumulation was also reduced. Subsequent analyses showed that co-consumption of Euglena with vegetables reduced adipocyte area, suppressed the expression of genes related to fatty acid synthesis and increased the expression of genes related to adipocyte growth and lipolysis. Therefore, co-consumption of Euglena with vegetables enhanced its anti-inflammatory effect and the inhibitory effect on visceral fat accumulation likely by modulating the composition of gut microbiota.

Morbid obesity and hypertension: The role of perirenal fat.

Accumulation of fat in renal sinus and hilum is associated with hypertension development. We evaluated the relationship between perirenal fat and hypertension in a population of morbidly obese patients and the potential variations after sleeve-gastrectomy. Two hundred and eighty-four morbidly obese patients were included in the study, and 126 underwent sleeve-gastrectomy. At baseline and 10-12 months after surgery, we evaluated anthropometric parameters, blood pressure, glycometabolic, and lipidic assessment, and performed an ultrasonographic evaluation of visceral fat area and perirenal fat thickness. The perirenal fat thickness in hypertensive obese was higher than in nonhypertensive (13.6 ± 4.8 vs 11.6 ± 4.1, P = 0.001). It showed a significant direct correlation with age, waist circumference, BMI, systolic blood pressure (SBP), insulinemia, HOMA-IR, glycated hemoglobin, and creatinine. The independent predictors (R2  = 0.129) of SBP were perirenal fat thickness (ß = 0.160, P = 0.022) and age (ß = 0.175, P = 0.011). After surgery, perirenal fat thickness significantly decreased (from 13 ± 4 to 9 ± 4 mm, P <0.001). In the 89 hypertensive obese patients who underwent sleeve-gastrectomy, we observed a significant decrease in antihypertensive medications needed. Sixteen patients suspended therapy. The perirenal fat thickness in obese patients could be a valuable tool to define the risk of developing hypertension, providing the clinician with an additional parameter to define those who need a more aggressive treatment and could benefit most from bariatric surgery.

Fermented Soybean Suppresses Visceral Fat Accumulation in Mice.

SCOPE: Mice are fed a soybean diet before or after fermentation in the present work to allow direct comparison of the antiobesity effect of fermentation. METHODS: C57BL6J mice were fed high-fat diets containing boiled soybeans (prefermentation) or Natto (postfermentation) for 4 weeks. Prefermented cooked soybeans or Natto was added at levels of 2.5 and 5%, which are the amounts that can be ingested in a normal diet once and twice a day. In addition, mice gut microbiota from fecal samples were analyzed to explore the mechanisms of effects caused by fermentation. RESULTS: Natto intake significantly reduced visceral fat in a dose-dependent manner, inhibited hypertrophy of adipocytes, improved carbohydrate metabolism, and reduced oxidative stress. These effects were seen in mice fed soybeans before fermentation, but were stronger in mice fed Natto. Therefore, soybean intake has beneficial effects and fermentation of soybeans enhances these effects. Natto was found to suppress fatty acid synthesis and promote fatty acid catabolism in the liver. These effects were also stronger with Natto compared with soybeans before fermentation. In addition, Natto had more potent beneficial effects on gut microbiota compared to soybeans. CONCLUSIONS: These results suggest that Natto intake supports maintenance of health.

Deregulation of obesity-relevant genes is associated with progression in BMI and the amount of adipose tissue in pigs.

The aim of this study was to elucidate the relative impact of three phenotypes often used to characterize obesity on perturbation of molecular pathways involved in obesity. The three obesity-related phenotypes are (1) body mass index (BMI), (2) amount of subcutaneous adipose tissue (SATa), and (3) amount of retroperitoneal adipose tissue (RPATa). Although it is generally accepted that increasing amount of RPATa is 'unhealthy', a direct comparison of the relative impact of the three obesity-related phenotypes on gene expression has, to our knowledge, not been performed previously. We have used multiple linear models to analyze altered gene expression of selected obesity-related genes in tissues collected from 19 female pigs phenotypically characterized with respect to the obesity-related phenotypes. Gene expression was assessed by high-throughput qPCR in RNA from liver, skeletal muscle and abdominal adipose tissue. The stringent statistical approach used in the study has increased the power of the analysis compared to the classical approach of analysis in divergent groups of individuals. Our approach led to the identification of key components of cellular pathways that are modulated in the three tissues in association with changes in the three obesity-relevant phenotypes (BMI, SATa and RPATa). The deregulated pathways are involved in biosynthesis and transcript regulation in adipocytes, in lipid transport, lipolysis and metabolism, and in inflammatory responses. Deregulation seemed more comprehensive in liver (23 genes) compared to abdominal adipose tissue (10 genes) and muscle (3 genes). Notably, the study supports the notion that excess amount of intra-abdominal adipose tissue is associated with a greater metabolic disease risk. Our results provide molecular support for this notion by demonstrating that increasing amount of RPATa has a higher impact on perturbation of cellular pathways influencing obesity and obesity-related metabolic traits compared to increase in BMI and amount of SATa.

Developmental Programming: Impact of Prenatal Testosterone Excess on Steroidal Machinery and Cell Differentiation Markers in Visceral Adipocytes of Female Sheep.

Prenatal testosterone (T)-treated female sheep manifest reduced adipocyte size and peripheral insulin resistance. The small adipocyte phenotype may reflect defects in adipogenesis and its steroidal machinery. To test whether prenatal T treatment from gestational days 30 to 90 alters the visceral adipose tissue (VAT) steroidal machinery and reduces adipocyte differentiation, we examined expression of the steroidogenic enzymes, steroid receptors, and adipocyte differentiation markers at fetal day 90 and postnatal ages 10 and 21 months. Because gestational T treatment increases fetal T and maternal insulin, the contributions of these were assessed by androgen receptor antagonist or insulin sensitizer cotreatment, either separately (at fetal day 90 and 21 months of age time points) or together (10 months of age). The effects on adipogenesis were assessed in the VAT-derived mesenchymal stem cells (AT-MSCs) from pre- and postpubertal time points to evaluate the effects of pubertal steroidal changes on adipogenesis. Our results show that VAT manifests potentially a predominant estrogenic intracrine milieu (increased aromatase and estrogen receptor α) and reduced differentiation markers at fetal day 90 and postnatal 21 months of age. These changes appear to involve both androgenic and metabolic pathways. Preliminary findings suggest that prenatal T treatment reduces adipogenesis, decreases expression of differentiation, and increases expression of commitment markers at both pre- and postpubertal time points. Together, these findings suggest that (1) increased commitment of AT-MSCs to adipocyte lineage and decreased differentiation to adipocytes may underlie the small adipocyte phenotype of prenatal T-treated females and (2) excess T-induced changes in steroidal machinery in the VAT likely participate in the programming/maintenance of this defect.

Reduced body weight gain in ubiquilin-1 transgenic mice is associated with increased expression of energy-sensing proteins.

Ubiquilin-1 (Ubqln1), a ubiquitin-like protein, is implicated in a variety of pathophysiological processes, but its role in mediating body weight gain or metabolism has not been determined. Here, we demonstrate that global overexpression of Ubqln1 in a transgenic (Tg) mouse reduces the animal's body weight gain. The decreased body weight gain in Tg mice is associated with lower visceral fat content and higher metabolic rate. The Ubqln1 Tg mice exhibited reduced leptin and insulin levels as well as increased insulin sensitivity manifested by homeostatic model assessment of insulin resistance. Additionally, the reduced body weight in Tg mice was associated with the upregulation of two energy-sensing proteins, sirtuin1 (SIRT1) in the hypothalamus and AMP-activated protein kinase (AMPK) in the skeletal muscle. Consistent with the in vivo results, overexpression of Ubqln1 significantly increased SIRT1 and AMPK levels in the mouse embryonic fibroblast cell culture. Thus, our results not only establish the link between Ubqln1 and body weight regulation but also indicate that the metabolic function of Ubqln1 on body weight may be through regulating energy-sensing proteins.

Genetic improvement of feed conversion ratio via indirect selection against lipid deposition in farmed rainbow trout (Oncorhynchus mykiss Walbaum).

In farmed fish, selective breeding for feed conversion ratio (FCR) may be possible via indirectly selecting for easily-measured indicator traits correlated with FCR. We tested the hypothesis that rainbow trout with low lipid% have genetically better FCR, and that lipid% may be genetically related to retention efficiency of macronutrients, making lipid% a useful indicator trait. A quantitative genetic analysis was used to quantify the benefit of replacing feed intake in a selection index with one of three lipid traits: body lipid%, muscle lipid% or viscera% weight of total body weight (reflecting visceral lipid). The index theory calculations showed that simultaneous selection for weight gain and against feed intake (direct selection to improve FCR) increased the expected genetic response in FCR by 1·50-fold compared with the sole selection for growth. Replacing feed intake in the selection index with body lipid%, muscle lipid% or viscera% increased genetic response in FCR by 1·29-, 1·49- and 1·02-fold, respectively, compared with the sole selection for growth. Consequently, indirect selection for weight gain and against muscle lipid% was almost as effective as direct selection for FCR. Fish with genetically low body and muscle lipid% were more efficient in turning ingested protein into protein weight gain. Both physiological and genetic mechanisms promote the hypothesis that low-lipid% fish are more efficient. These results highlight that in breeding programmes of rainbow trout, control of lipid deposition improves not only FCR but also protein-retention efficiency. This improves resource efficiency of aquaculture and reduces nutrient load to the environment.

Light-intensity and high-intensity interval training improve cardiometabolic health in rats.

Physical activity has the potential to reduce cardiometabolic risk factors but evaluation of different intensities of physical activity and the mechanisms behind their health effects still need to be fully established. This study examined the effects of sedentary behaviour, light-intensity training, and high-intensity interval training on biometric indices, glucose and lipid metabolism, inflammatory and oxidative stress markers, and vascular and cardiac function in adult rats. Rats (12 weeks old) were randomly assigned to 1 of 4 groups: control (CTL; no exercise), sedentary (SED; no exercise and housed in small cages to reduce activity), light-intensity trained (LIT; four 30-min exercise bouts/day at 8 m/min separated by 2-h rest period, 5 days/week), and high-intensity interval trained (HIIT, four 2.5-min work bouts/day at 50 m/min separated by 3-min rest periods, 5 days/week). After 12 weeks of intervention, SED had greater visceral fat accumulation (p < 0.01) and slower cardiac conduction (p = 0.04) compared with the CTL group. LIT and HIIT demonstrated beneficial changes in body weight, visceral and epididymal fat weight, glucose regulation, low-density lipoprotein cholesterol, total cholesterol, and mesenteric vessel contractile response compared with the CTL group (p < 0.05). LIT had significant improvements in insulin sensitivity and cardiac conduction compared with the CTL and SED groups whilst HIIT had significant improvements in systolic blood pressure and endothelium-independent vasodilation to aorta and mesenteric artery compared with the CTL group (p < 0.05). LIT and HIIT induce health benefits by improving traditional cardiometabolic risk factors. LIT improves cardiac health while HIIT promotes improvements in vascular health.

ADAMTS5 promotes murine adipogenesis and visceral adipose tissue expansion.

Enhanced expression of the aggrecanase ADAMTS5 (A Disintegrin And Metalloproteinase with Thrombospondin type 1 motifs; member 5) has been observed in adipose tissue (AT) of obese rodents. Here, we have investigated the role of ADAMTS5 in adipogenesis, AT expansion and associated angiogenesis. In vitro differentiation of precursor cells into mature adipocytes was studied using murine embryonic fibroblasts (MEF) derived from wild-type (Adamts5(+/+)) and ADAMTS5 deficient (Adamts5(-/-)) mice, or 3T3-F442A preadipocytes with stable gene silencing of Adamts5. De novo adipogenesis was monitored by injection of 3T3-F442A cells with or without Adamts5 knockdown in Nude mice. Furthermore, Adamts5(+/+)and Adamts5(-/-) mice were kept on a high-fat diet (HFD) to monitor AT development. Adamts5(-/-) MEF, as well as 3T3-F442A preadipocytes with Adamts5 knockdown, showed significantly reduced differentiation as compared to control cells. In mice, de novo formed fat pads arising from 3T3-F442A cells with Adamts5 knockdown were significantly smaller as compared to controls. After 15 or 25 weeks on HFD, total body weight and subcutaneous AT weight were similar for Adamts5(+/+) and Adamts5(-/-) mice, but visceral/gonadal fat mass was significantly lower for Adamts5(-/-) mice. These data were confirmed by magnetic resonance imaging. In addition, the blood vessel density in adipose tissue was higher for Adamts5(-/-) mice kept on HFD. In conclusion, our data support the concept that ADAMTS5 promotes adipogenesis in vitro and in vivo, as well as development of visceral AT and associated angiogenesis in mice kept on HFD.

Regulation of adipogenesis by paracrine factors from adipose stromal-vascular fraction - a link to fat depot-specific differences.

Visceral and subcutaneous adipose tissue depots have distinct features and contribute differentially to the development of metabolic dysfunction. We show here that adipocyte differentiation in subcutaneous stromal-vascular fraction (SVF) is increased compared to visceral SVF, however this increased differentiation capacity seems not to be due to changes in the number of adipocyte precursor cells. Rather, we demonstrate that secreted heat-sensitive factors from the SVF can inhibit adipocyte differentiation and that this effect is higher in visceral than in subcutaneous SVF, suggesting that visceral SVF is a source of secreted factors that can inhibit adipocyte formation. In order to explore secreted proteins that potentially inhibit differentiation in visceral preadipocytes we analyzed the secretome of both SVFs which led to the identification of 113 secreted proteins with an overlap of 42%. Further expression analysis in both depots revealed 16 candidates that were subsequently analyzed in a differentiation screen using an adenoviral knockdown system. From this analysis we were able to identify two potential inhibitory candidates, namely decorin (Dcn) and Sparc-like 1 (Sparcl1). We could show that ablation of either candidate enhanced adipogenesis in visceral preadipocytes, while treatment of primary cultures with recombinant Sparcl1 and Dcn blocked adipogenesis in a dose dependent manner. In conclusion, our data suggests that the differences in adipogenesis between depots might be due to paracrine and autocrine feedback mechanisms which could in turn contribute to metabolic homeostasis.