61 research outputs found
Characterisation of receptor-specific TNFα functions in adipocyte cell lines lacking type 1 and 2 TNF receptors
No full textAbstractTumour necrosis factor-alpha (TNFα) is a multifunctional cytokine that exerts a myriad of biological actions in numerous different tissues including adipocytes through its two distinct cell surface receptors. To address the role of each TNF receptor in the biological actions of TNFα in adipocytes, we have developed four new preadipocyte cell lines. These were established from wild type controls (TNFR1+/+R2+/+) and from mice lacking TNFR1 (TNFR1−/−), TNFR2 (TNFR2−/−) or both (TNFR1−/−R2−/−). All four new cell lines can fully differentiate to form mature adipocytes, under appropriate culture conditions, as judged by cell morphology, expression of multiple adipogenic markers and the ability to mediate agonist-stimulated lipolysis and insulin-stimulated glucose transport. In wild type (TNFR1+/+R2+/+) and TNFR2−/− adipocytes, TNFα stimulated lipolysis and inhibited insulin-stimulated glucose transport as well as insulin receptor autophosphorylation. In contrast, these activities were completely lost in the TNFR1−/−R2−/− and TNFR1−/− cells. Taken together, these studies demonstrate that TNFα-induced lipolysis, as well as inhibition of insulin-stimulated glucose transport are predominantly mediated by TNFR1 and that the presence of TNFR2 is not necessary for these functions. This new experimental system promises to be useful in dissecting the molecular pathways activated by each TNF receptor in mediating the biological functions of TNFα in differentiated adipocytes
Organ-specific role of the lipogenic transcription factor ChREBP for metabolic adaptation in response to cold exposure and its implications for metabolic diseases
No full textEver since the discovery of active and adequate brown fat depots in adult humans, non-shivering thermogenesis (NST) function of brown adipose tissue (BAT), where oxidation of tissue-stored fats is uncoupled from ATP synthesis and instead used to generate heat for the body, has become a promising avenue for metabolic disease research in the last decade. As BAT utilizes its stored fats for the purpose of generating heat for the body, it also maintains a stable energy storage in the form of fats within brown adipocytes. To prevent replenishment of these fat stores, upon cold stimuli, BAT picks up additional glucose from plasma to be converted into storage triglycerides via de novo lipogenesis (DNL), alongside taking up additional lipids also from plasma. If the cold stimuli are long enough, the same phenomena are observed in white adipose tissue (WAT) as well via a process called browning. These trends make BAT, NST and WAT browning exciting avenues for metabolic disease research targeting type 2 diabetes and obesity, alongside fatty liver diseases and other metabolic conditions. ChREBP, as a glycolytic and lipogenic transcription factor identified more than a decade ago, has been established to be the main driver of DNL in adipocytes and thus has important roles in the processes observed in BAT and WAT during NST and browning, which can have far-reaching implications. The present thesis work evaluates effects and necessity of ChREBP function by analysing its organ-specific roles during metabolic adaptation to cold, in liver, BAT, and WAT via gene expression, protein expression, and tissue uptake data obtained from murine cohorts with ChREBP availability versus deletion, housed under different ambient temperatures.Biochemical EngineeringBSc/B
Higher-dimensional absolute versions of symmetric, Frobenius, and quasi-Frobenius algebras
No full textIn this paper, we define and discuss higher-dimensional and absolute versions of symmetric, Frobenius, and quasi-Frobenius algebras. In particular, we compare these with the relative notions defined by Scheja and Storch. We also prove the validity of codimension two-argument for modules over a coherent sheaf of algebras with a 2-canonical module, generalizing a result of the author
Higher-dimensional absolute versions of symmetric, Frobenius, and quasi-Frobenius algebras
No full textIn this paper, we define and discuss higher-dimensional and absolute versions of symmetric, Frobenius, and quasi-Frobenius algebras. In particular, we compare these with the relative notions defined by Scheja and Storch. We also prove the validity of codimension two-argument for modules over a coherent sheaf of algebras with a 2-canonical module, generalizing a result of the author
Beneficial effects of IKKε-deficiency on body weight and insulin sensitivity are lost in high fat diet-induced obesity in mice
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