Daniel Lindén
Publications 45
#1Alba Carreras (Sahlgrenska University Hospital)H-Index: 4
#2Luna Simona PaneH-Index: 2
Last.Marcello MarescaH-Index: 6
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Background Plasma concentration of low-density lipoprotein (LDL) cholesterol is a well-established risk factor for cardiovascular disease. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), which regulates cholesterol homeostasis, has recently emerged as an approach to reduce cholesterol levels. The development of humanized animal models is an important step to validate and study human drug targets, and use of genome and base editing has been proposed as a mean to target diseas...
1 CitationsSource
#1Sebastian Prill (AstraZeneca)H-Index: 1
#2Andrea Caddeo (University of Gothenburg)H-Index: 3
Last.Stefano Romeo (University of Gothenburg)H-Index: 41
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There is a high unmet need for developing treatments for nonalcoholic fatty liver disease (NAFLD), for which there are no approved drugs today. Here, we used a human in vitro disease model to understand mechanisms linked to genetic risk variants associated with NAFLD. The model is based on 3D spheroids from primary human hepatocytes from five different donors. Across these donors, we observed highly reproducible differences in the extent of steatosis induction, demonstrating that inter-donor var...
2 CitationsSource
#1Stephen Lee (UCLA: University of California, Los Angeles)H-Index: 27
#2Christina Priest (UCLA: University of California, Los Angeles)H-Index: 1
Last.Cynthia Hong (UCLA: University of California, Los Angeles)H-Index: 31
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Liver X receptors limit cellular lipid uptake by stimulating the transcription of inducible degrader of the low-density lipoprotein receptor (IDOL), an E3 ubiquitin ligase that targets lipoprotein receptors for degradation. The function of IDOL in systemic metabolism is incompletely understood. Here we show that loss of IDOL in mice protects against the development of diet-induced obesity and metabolic dysfunction by altering food intake and thermogenesis. Unexpectedly, analysis of tissue-specif...
#1Tobias KroonH-Index: 4
Last.Kristina WalleniusH-Index: 14
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#1Vilborg Palsdottir (University of Gothenburg)H-Index: 9
#2Sara H Windahl (KI: Karolinska Institutet)H-Index: 24
Last.Claes Ohlsson (University of Gothenburg)H-Index: 90
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Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in western countries. Despite the high prevalence of NAFLD, the underlying biology of the disease progression is not clear, and there are no approved drugs to treat non-alcoholic steatohepatitis (NASH), the most advanced form of the disease. Thus, there is an urgent need for developing advanced in vitro human cellular systems to study disease mechanisms and drug responses. We attempted to create an organoid system geneti...
1 CitationsSource
#1Daniel Lindén (AstraZeneca)H-Index: 19
#2Andrea Ahnmark (AstraZeneca)H-Index: 8
Last.Stefano Romeo (Magna Græcia University)H-Index: 41
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Abstract Objective Nonalcoholic fatty liver disease (NAFLD) is becoming a leading cause of advanced chronic liver disease. The progression of NAFLD, including nonalcoholic steatohepatitis (NASH), has a strong genetic component, and the most robust contributor is the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 encoding the 148M protein sequence variant. We hypothesized that suppressing the expression of the PNPLA3 148M mutant protein would exert a beneficial effect on the ent...
9 CitationsSource
#1Nicholas Buss (MedImmune)H-Index: 2
#2Jean-Martin Lapointe (MedImmune)H-Index: 1
Last.Daniel Lindén (AstraZeneca)H-Index: 19
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Abstract Fibroblast Growth Factors (FGFs) and their receptors (FGFRs) have been proposed as potential drug targets for the treatment of obesity. The aim of this study was to assess the potential toxicity in rats of three anti-FGFR1c mAbs with differential binding activity prior to clinical development. Groups of male rats received weekly injections of either one of two FGFR1c-specific mAbs or an FGFR1c/FGFR4-specific mAb at 10 mg/kg for up to 4 weeks. All three mAbs caused significant reductions...
1 CitationsSource
#1Fanny Langlet (Columbia University)H-Index: 17
#2Rebecca A. Haeusler (Columbia University)H-Index: 15
Last.Domenico Accili (Columbia University)H-Index: 70
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Insulin resistance is a hallmark of diabetes and an unmet clinical need. Insulin inhibits hepatic glucose production and promotes lipogenesis by suppressing FOXO1-dependent activation of G6pase and inhibition of glucokinase, respectively. The tight coupling of these events poses a dual conundrum: mechanistically, as the FOXO1 corepressor of glucokinase is unknown, and clinically, as inhibition of glucose production is predicted to increase lipogenesis. Here, we report that SIN3A is the insulin-s...
34 CitationsSource
#1Peter GennemarkH-Index: 10
#2M Trägårdh (Warw.: University of Warwick)H-Index: 1
Last.Madeleine AntonssonH-Index: 11
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In this study, we present the translational modeling used in the discovery of AZD1979, a melanin-concentrating hormone receptor 1 (MCHr1) antagonist aimed for treatment of obesity. The model quantitatively connects the relevant biomarkers and thereby closes the scaling path from rodent to man, as well as from dose to effect level. The complexity of individual modeling steps depends on the quality and quantity of data as well as the prior information; from semimechanistic body-composition models ...
2 CitationsSource