Recent CIG publications Archive

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Diabetologia.: co-auth.: B.Thorens

 2019 Jun 13. doi: 10.1007/s00125-019-4911-4. [Epub ahead of print]

Fostering improved human islet research: a European perspective.

KEYWORDS:

Beta cells; Diabetes research; Human islets

PMID: 31197398

 

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Dev Neurobiol.: auth.: group Herr

 2019 Jun 17. doi: 10.1002/dneu.22704. [Epub ahead of print]

Cortical and commissural defects upon HCF-1 loss in Nkx2.1-derived embryonic neurons and glia.

Abstract

Formation of the cerebral cortex and commissures involves a complex developmental process defined by multiple molecular mechanisms governing proliferation of neuronal and glial precursors, neuronal and glial migration, and patterning events. Failure in any of these processes can lead to malformations. Here, we study the role of HCF-1 in these processes. HCF-1 is a conserved metazoan transcriptional co-regulator long implicated in cell proliferation and more recently in human metabolic disorders and mental retardation. Loss of HCF-1 in a subset of ventral telencephalic Nkx2.1-positive progenitors leads to reduced numbers of GABAergic interneurons and glia, owing not to decreased proliferation but rather to increased apoptosis before cell migration. The loss of these cells leads to development of severe commissural and cortical defects in early postnatal mouse brains. These defects include mild and severe structural defects of the corpus callosum and anterior commissure, respectively, and increased folding of the cortex resembling polymicrogyria. Hence, in addition to its well-established role in cell proliferation, HCF-1 is important for organ development, here the brain. This article is protected by copyright. All rights reserved.

KEYWORDS:

GABAergic neurons; Nkx2.1; anterior commissure; corpus callosum; cortex; glia; polymicrogyria

PMID: 31207118

 

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Cardiovasc Diabetol.: co-auth.: W. Wahli

 2019 Jun 4;18(1):71. doi: 10.1186/s12933-019-0864-7.

The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential : A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation.

Abstract

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.

KEYWORDS:

Atherogenic dyslipidemia; Diabetes; Inflammation; PROMINENT; Pemafibrate (K-877); Remnant cholesterol; Residual cardiovascular risk; SPPARMalpha; Selective peroxisome proliferator-activated receptor alpha modulator; Triglycerides; Visceral obesity

PMID: 31164165
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Diabetes Metab.: co-auth.: W. Wahli

 2019 Jun 1. pii: S1262-3636(19)30088-6. doi: 10.1016/j.diabet.2019.05.005. [Epub ahead of print]

Regulation of hepatokine gene expression in response to fasting and feeding: Influence of PPAR-α and insulin-dependent signalling in hepatocytes.

Abstract

AIM:

– In hepatocytes, the peroxisome proliferator-activated receptor (PPAR)-α and insulin receptor (IR) are critical for transcriptional responses to fasting and feeding, respectively. The present report analyzes the effects of nutritional status (fasting vs feeding) on the expression of a large panel of hepatokines in hepatocyte-specific PPAR-α (Pparα hep-/-) and IR (IRhep-/-) null mice.

METHODS:

– Pparαhep-/- and IRhep-/- mice, and their wild-type littermates, were subjected to fasting or feeding metabolic challenges, then analyzed for hepatokine gene expression. Experiments were conducted in mice of both genders.

RESULTS:

– Our data confirmed that PPAR-α is essential for regulating fasting-induced Fgf21 and Angptl4 expression. In mice lacking PPAR-α, fasting led to increased Igfbp1 and Gdf15 gene expression. In the absence of hepatic IR, feeding induced overexpression of Igfbp1, follistatin (Fst) and adropin (Enho), and reduced activin E (Inhbe) expression. Gender had only a modest influence on hepatokine gene expression in the liver.

CONCLUSION:

– The present results highlight the potential roles of hepatokines as a class of hormones that substantially influence nutritional regulation in both female and male mice.

KEYWORDS:

Hepatokines; Insulin receptor; Nutritional regulation; PPAR-α

PMID: 31163275
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Curr Biol.: co-auth.: C.Dessimoz

 2019 May 16. pii: S0960-9822(19)30407-5. doi: 10.1016/j.cub.2019.04.009. [Epub ahead of print]

Mitigating Anticipated Effects of Systematic Errors Supports Sister-Group Relationship between Xenacoelomorpha and Ambulacraria.

Abstract

Xenoturbella and the acoelomorph worms (Xenacoelomorpha) are simple marine animals with controversial affinities. They have been placed as the sister group of all other bilaterian animals (Nephrozoa hypothesis), implying their simplicity is an ancient characteristic [1, 2]; alternatively, they have been linked to the complex Ambulacraria (echinoderms and hemichordates) in a clade called the Xenambulacraria [3-5], suggesting their simplicity evolved by reduction from a complex ancestor. The difficulty resolving this problem implies the phylogenetic signal supporting the correct solution is weak and affected by inadequate modeling, creating a misleading non-phylogenetic signal. The idea that the Nephrozoa hypothesis might be an artifact is prompted by the faster molecular evolutionary rate observed within the Acoelomorpha. Unequal rates of evolution are known to result in the systematic artifact of long branch attraction, which would be predicted to result in an attraction between long-branch acoelomorphs and the outgroup, pulling them toward the root [6]. Other biases inadequately accommodated by the models used can also have strong effects, exacerbated in the context of short internal branches and long terminal branches [7]. We have assembled a large and informative dataset to address this problem. Analyses designed to reduce or to emphasize misleading signals show the Nephrozoa hypothesis is supported under conditions expected to exacerbate errors, and the Xenambulacraria hypothesis is preferred in conditions designed to reduce errors. Our reanalyses of two other recently published datasets [1, 2] produce the same result. We conclude that the Xenacoelomorpha are simplified relatives of the Ambulacraria.

PMID: 31104936

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Front Endocrinol (Lausanne).: F. Langlet

 2019 May 7;10:286. doi: 10.3389/fendo.2019.00286. eCollection 2019.

Tanycyte Gene Expression Dynamics in the Regulation of Energy Homeostasis.

Abstract

Animal survival relies on a constant balance between energy supply and energy expenditure, which is controlled by several neuroendocrine functions that integrate metabolic information and adapt the response of the organism to physiological demands. Polarized ependymoglial cells lining the floor of the third ventricle and sending a single process within metabolic hypothalamic parenchyma, tanycytes are henceforth described as key components of the hypothalamic neural network controlling energy balance. Their strategic position and peculiar properties convey them diverse physiological functions ranging from blood/brain traffic controllers, metabolic modulators, and neural stem/progenitor cells. At the molecular level, these functions rely on an accurate regulation of gene expression. Indeed, tanycytes are characterized by their own molecular signature which is mostly associated to their diverse physiological functions, and the detection of variations in nutrient/hormone levels leads to an adequate modulation of genetic profile in order to ensure energy homeostasis. The aim of this review is to summarize recent knowledge on the nutritional control of tanycyte gene expression.

KEYWORDS:

energy balance; gene expression; hypothalamus; metabolic sensing; tanycyte

PMID: 31133987