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Removal of intra-abdominal visceral adipose tissue improves glucose tolerance in rats: role of hepatic triglyceride storage.

ABSTRACT: Epidemiological studies have demonstrated a strong link between increased visceral fat and metabolic syndrome. In rodents, removal of intra-abdominal but non-visceral fat improves insulin sensitivity and glucose homeostasis, though previous studies make an imprecise comparison to human physiology because actual visceral fat was not removed. We hypothesize that nutrient release from visceral adipose tissue may have greater consequences on metabolic regulation than nutrient release from non-visceral adipose depots since the latter drains into systemic but not portal circulation. To assess this we surgically decreased visceral white adipose tissue (~0.5 g VWATx) and compared the effects to removal of non-visceral epididymal fat (~4 g; EWATx), combination removal of visceral and non-visceral fat (~4.5 g; EWATx/VWATx) and sham-operated controls, in chow-fed rats. At 8 weeks after surgery, only the groups with visceral fat removed had a significantly improved glucose tolerance, although 8 times more fat was removed in EWATx compared with VWATx. This suggests that mechanisms controlling glucose metabolism are relatively more sensitive to reductions in visceral adipose tissue mass. Groups with visceral fat removed also had significantly decreased hepatic lipoprotein lipase (LPL) and triglyceride content compared with controls, while carnitine palmitoyltransferase (CPT-1A) was decreased in all fat-removal groups. In a preliminary experiment, we assessed the opposite hypothesis; i.e., we transplanted excess visceral fat from a donor rat to the visceral cavity (omentum and mesentery), which drains into the hepatic portal vein, of a recipient rat but observed no major metabolic effect. Overall, our results indicate surgical removal of intra-abdominal fat improves glucose tolerance through mechanism that may be mediated by reductions in liver triglyceride.

SUBMITTER: Foster MT

PROVIDER: S-EPMC3183256 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Removal of intra-abdominal visceral adipose tissue improves glucose tolerance in rats: role of hepatic triglyceride storage.

Foster Michelle T MT Shi Haifei H Seeley Randy J RJ Woods Stephen C SC

Physiology & behavior 20110612 5

Epidemiological studies have demonstrated a strong link between increased visceral fat and metabolic syndrome. In rodents, removal of intra-abdominal but non-visceral fat improves insulin sensitivity and glucose homeostasis, though previous studies make an imprecise comparison to human physiology because actual visceral fat was not removed. We hypothesize that nutrient release from visceral adipose tissue may have greater consequences on metabolic regulation than nutrient release from non-viscer ...[more]

PMID: 21683727

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Project description:Background & aimsWe compared fat storage in the abdominal region among individuals from 5 different ethnic-racial groups to determine whether fat storage is associated with disparities observed in metabolic syndrome and other obesity-associated diseases.MethodsWe collected data from 1794 participants in the Multiethnic Cohort Study (60-77 years old; of African, European [white], Japanese, Latino, or Native Hawaiian ancestry) with body mass index values of 17.1-46.2 kg/m2. From May 2013 through April 2016, participants visited the study clinic to undergo body measurements, an interview, and a blood collection. Participants were evaluated by dual-energy x-ray absorptiometry and abdominal magnetic resonance imaging. Among ethnic groups, we compared adiposity of the trunk, intra-abdominal visceral cavity, and liver, adjusting for total fat mass; we evaluated the association of adult weight change with abdominal adiposity; and we examined the prevalence of metabolic syndrome mediated by abdominal adiposity.ResultsRelative amounts of trunk, visceral, and liver fat varied significantly with ethnicity-they were highest in Japanese Americans, lowest in African Americans, and intermediate in the other groups. Compared with African Americans, the mean visceral fat area was 45% and 73% greater in Japanese American men and women, respectively, and the mean measurements of liver fat were 61% and 122% greater in Japanese American men and women. The visceral and hepatic adiposity associated with weight gain since participants were 21 years old varied in a similar pattern among ethnic-racial groups. In the mediation analysis, visceral and liver fat jointly accounted for a statistically significant fraction of the difference in metabolic syndrome prevalence, compared with white persons, for African Americans, Japanese Americans, and Native Hawaiian women, independently of total fat mass.ConclusionsIn an analysis of data from the participants in the Multiethnic Cohort Study, we found extensive differences among ethnic-racial groups in the propensity to store fat intra-abdominally. This observation should be considered by clinicians in the prevention and early detection of metabolic disorders.

Project description:IntroductionIntra-abdominal hypertension (IAH) causes atelectasis, reduces lung volumes and increases respiratory system elastance. Positive end-expiratory pressure (PEEP) in the setting of IAH and healthy lungs improves lung volumes but not oxygenation. However, critically ill patients with IAH often suffer from acute lung injury (ALI). This study, therefore, examined the respiratory and cardiac effects of positive end-expiratory pressure in an animal model of IAH, with sick lungs.MethodsNine pigs were anesthetized and ventilated (48 +/- 6 kg). Lung injury was induced with oleic acid. Three levels of intra-abdominal pressure (baseline, 18, and 22 mmHg) were randomly generated. At each level of intra-abdominal pressure, three levels of PEEP were randomly applied: baseline (5 cmH2O), moderate (0.5 × intra-abdominal pressure), and high (1.0 × intra-abdominal pressure). We measured end-expiratory lung volumes, arterial oxygen levels, respiratory mechanics, and cardiac output 10 minutes after each new IAP and PEEP setting.ResultsAt baseline PEEP, IAH (22 mmHg) decreased oxygen levels (-55%, P <0.001) and end-expiratory lung volumes (-45%, P = 0.007). At IAP of 22 mmHg, moderate and high PEEP increased oxygen levels (+60%, P = 0.04 and +162%, P <0.001) and end-expiratory lung volume (+44%, P = 0.02 and +279%, P <0.001) and high PEEP reduced cardiac output (-30%, P = 0.04). Shunt and dead-space fraction inversely correlated with oxygen levels and end-expiratory lung volumes. In the presence of IAH, lung, chest wall and respiratory system elastance increased. Subsequently, PEEP decreased respiratory system elastance by decreasing chest wall elastance.ConclusionsIn a porcine sick lung model of IAH, PEEP matched to intra-abdominal pressure led to increased lung volumes and oxygenation and decreased chest wall elastance shunt and dead-space fraction. High PEEP decreased cardiac output. The study shows that lung injury influences the effects of IAH and PEEP on oxygenation and respiratory mechanics. Our findings support the application of PEEP in the setting of acute lung injury and IAH.

Project description:Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio, our most significant p-value was rs11118316 at LYPLAL1 gene (p = 3.1 × 10E-09), previously identified in association with waist-hip ratio. For SAT, the most significant SNP was in the FTO gene (p = 5.9 × 10E-08). Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6 × 10-08), but not men (p = 0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006) but not men (p = 0.24) for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]). Finally, we interrogated our data for the 14 recently published loci for body fat distribution (measured by waist-hip ratio adjusted for BMI); associations were observed at 7 of these loci. In contrast, we observed associations at only 7/32 loci previously identified in association with BMI; the majority of overlap was observed with SAT. Genome-wide association for visceral and subcutaneous fat revealed a SNP for VAT in women. More refined phenotypes for body composition and fat distribution can detect new loci not previously uncovered in large-scale GWAS of anthropometric traits.

Dataset Information

Removal of intra-abdominal visceral adipose tissue improves glucose tolerance in rats: role of hepatic triglyceride storage.

Publications

Removal of intra-abdominal visceral adipose tissue improves glucose tolerance in rats: role of hepatic triglyceride storage.

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