Dataset Information

The multi-level action of fatty acids on adiponectin production by fat cells.

ABSTRACT: Current epidemics of diabetes mellitus is largely caused by wide spread obesity. The best-established connection between obesity and insulin resistance is the elevated and/or dysregulated levels of circulating free fatty acids that cause and aggravate insulin resistance, type 2 diabetes, cardiovascular disease and other hazardous metabolic conditions. Here, we investigated the effect of a major dietary saturated fatty acid, palmitate, on the insulin-sensitizing adipokine adiponectin produced by cultured adipocytes. We have found that palmitate rapidly inhibits transcription of the adiponectin gene and the release of adiponectin from adipocytes. Adiponectin gene expression is controlled primarily by PPAR? and C/EBP?. Using mouse embryonic fibroblasts from C/EBP?-null mice, we have determined that the latter transcription factor may not solely mediate the inhibitory effect of palmitate on adiponectin transcription leaving PPAR? as a likely target of palmitate. In agreement with this model, palmitate increases phosphorylation of PPAR? on Ser273, and substitution of PPAR? for the unphosphorylated mutant Ser273Ala blocks the effect of palmitate on adiponectin transcription. The inhibitory effect of palmitate on adiponectin gene expression requires its intracellular metabolism via the acyl-CoA synthetase 1-mediated pathway. In addition, we found that palmitate stimulates degradation of intracellular adiponectin by lysosomes, and the lysosomal inhibitor, chloroquine, suppressed the effect of palmitate on adiponectin release from adipocytes. We present evidence suggesting that the intracellular sorting receptor, sortilin, plays an important role in targeting of adiponectin to lysosomes. Thus, palmitate not only decreases adiponectin expression at the level of transcription but may also stimulate lysosomal degradation of newly synthesized adiponectin.

SUBMITTER: Karki S

PROVIDER: S-EPMC3226650 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The multi-level action of fatty acids on adiponectin production by fat cells.

Karki Shakun S Chakrabarti Partha P Huang Guanrong G Wang Hong H Farmer Stephen R SR Kandror Konstantin V KV

PloS one 20111129 11

Current epidemics of diabetes mellitus is largely caused by wide spread obesity. The best-established connection between obesity and insulin resistance is the elevated and/or dysregulated levels of circulating free fatty acids that cause and aggravate insulin resistance, type 2 diabetes, cardiovascular disease and other hazardous metabolic conditions. Here, we investigated the effect of a major dietary saturated fatty acid, palmitate, on the insulin-sensitizing adipokine adiponectin produced by ...[more]

PMID: 22140527

Similar Datasets

Project description:The economic value of milk fat and its responsiveness to management strategies provides strong interest in maximizing milk fat production by minimizing occurrence of biohydrogenation-induced milk fat depression (BH-MFD) and maximizing de novo synthesized fatty acids (FA). Tools that allow a timely diagnosis of BH-MFD would improve nutritional management. Specific milk FA or FA categories correlate to milk fat concentration and are of interest for diagnosing the cause of changes in milk fat concentration. The objective of the current study was to characterize the relationship between milk fat concentration and trans-10 C18:1, a proxy for BH-MFD, and FA <16 carbons that originate solely from de novo lipogenesis using a meta-analysis approach that used data from the literature and unpublished Penn State experiments. Prior to the meta-analysis, the effect of FA methylation method on milk FA profile was tested to determine potential bias between papers. There was no difference between sodium methoxide, acid, and acid-base methylation methods on trans-10 C18:1 concentration, but acid methods resulted in loss of short-chain FA. The relationship between trans-10 C18:1 and milk fat percentage was investigated using a 2-component model, where one component described the fraction unresponsive to BH-MFD and the other described a responsive fraction that is exponentially related to trans-10 C18:1. The 2 fractions where characterized utilizing a Bayesian hierarchical model accounting for between-study variability. The model was defined by the function f(x, θ1, θ2, θ3) = θ1 + θ2exp(θ3), where the unresponsive θ1 fraction was 2.15 ± 0.09%, the responsive θ2 fraction was 1.55 ± 0.08%, and the exponential term θ3 was -0.503 ± 0.07 (posterior mean ± posterior standard deviation from the Bayesian hierarchical model). A Lin's concordance correlation coefficient of 0.67 suggested good agreement between observations and predictions from the Bayesian hierarchical model, computed only with the model's mean population parameters. There was a linear relationship between milk fat concentration and FA <16 C as a percentage of total FA (intercept = 2.68 ± 0.237 and slope = 0.043 ± 0.011; coefficient of determination = 0.31). The relationship between milk FA <16 C and milk fat concentration is weaker than what has been published, likely because multiple factors can reduce de novo FA without reducing milk fat and the broad range of diets present in the literature.

Project description:BackgroundA broad diversity of natural and non-natural esters have now been made in bacteria, and in other microorganisms, as a result of original metabolic engineering approaches. However, the fact that the properties of these molecules, and therefore their applications, are largely defined by the structural features of the fatty acid and alcohol moieties, has driven a persistent interest in generating novel structures of these chemicals.ResultsIn this research, we engineered Escherichia coli to synthesize de novo esters composed of multi-methyl-branched-chain fatty acids and short branched-chain alcohols (BCA), from glucose and propionate. A coculture engineering strategy was developed to avoid metabolic burden generated by the reconstitution of long heterologous biosynthetic pathways. The cocultures were composed of two independently optimized E. coli strains, one dedicated to efficiently achieve the biosynthesis and release of the BCA, and the other to synthesize the multi methyl-branched fatty acid and the corresponding multi-methyl-branched esters (MBE) as the final products. Response surface methodology, a cost-efficient multivariate statistical technique, was used to empirical model the BCA-derived MBE production landscape of the coculture and to optimize its productivity. Compared with the monoculture strategy, the utilization of the designed coculture improved the BCA-derived MBE production in 45%. Finally, the coculture was scaled up in a high-cell density fed-batch fermentation in a 2 L bioreactor by fine-tuning the inoculation ratio between the two engineered E. coli strains.ConclusionPrevious work revealed that esters containing multiple methyl branches in their molecule present favorable physicochemical properties which are superior to those of linear esters. Here, we have successfully engineered an E. coli strain to broaden the diversity of these molecules by incorporating methyl branches also in the alcohol moiety. The limited production of these esters by a monoculture was considerable improved by a design of a coculture system and its optimization using response surface methodology. The possibility to scale-up this process was confirmed in high-cell density fed-batch fermentations.

Dataset Information

The multi-level action of fatty acids on adiponectin production by fat cells.

Publications

The multi-level action of fatty acids on adiponectin production by fat cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure