Carolina Hagberg - Academia.edu (original) (raw)

Papers by Carolina Hagberg

Nature Reviews Molecular Cell Biology, Dec 11, 2023

Apolipoprotein-B (APOB) containing lipoproteins are causative for atherosclerotic cardiovascular ... more Apolipoprotein-B (APOB) containing lipoproteins are causative for atherosclerotic cardiovascular disease. Whether the vasculature is the initial responding site or if atherogenic-dyslipidemia effects other organs simultaneously is unknown. We set out to discover how the liver responds to a dyslipidemic insult through the creation of inducible mouse models based on human familial hypercholesterolemia mutations andin vivotracing of APOB. An acute transition to atherogenic APOB-lipoprotein plasma levels resulted in rapid accumulation of triglycerides and cholesterol in the liver. Single cell RNA-seq and flow cytometry disclosed that multiple immune cells have the ability to engulf APOB-lipoproteins. However bulk RNA-seq of the liver revealed an inflammatory Kupffer cell-specific transcriptional program that could not be activated by a western diet alone. Depletion of Kupffer cells through clodronate liposomes or CD8 T cell targeting rapidly raised plasma lipoprotein levels, indicating ...

bioRxiv (Cold Spring Harbor Laboratory), Mar 19, 2024

The Journal of Physiology, Sep 6, 2021

Adipocyte enlargement is a key feature of obesity and associated with insulin resistance and meta... more Adipocyte enlargement is a key feature of obesity and associated with insulin resistance and metabolic disease The cause and consequences of adipocyte enlargement have remained hard to study in vitro due to a lack of human cell models with representative morphology This paper provides an easily set up spheroid culture method, HUVAS (human unilocular vascularized adipocyte spheroids), for the differentiation and culturing of human adipocytes with a more unilocular morphology We show that providing adipocyte progenitors with a vascular differentiation niche is key for achieving in vitro differentiated adipocytes with large lipid droplets Lipid treatment of the HUVAS spheroids can further adipocyte enlargement and induce cellular dysfunction, mimicking the in vivo effects of weight gain The model will allow a wider research community to perform mechanistic studies of the factors impacting on human adipocyte differentiation and growth, increasing our understanding of how obesity develops and why it has such detrimental consequences on whole body metabolism

Frontiers in Cell and Developmental Biology, Sep 15, 2022

Schematic showing the most important visceral and subcutaneous white adipose tissue depots in mic... more Schematic showing the most important visceral and subcutaneous white adipose tissue depots in mice (left) and humans (right), respectively. Enlarged simplified drawings of the respective tissue structures are merely indicative of the relative differences between depots, and do not include all details of the tissue itself.

Frontiers in Research Metrics and Analytics, May 10, 2021

Expectations of fair competition underlie the assumption that academia is a meritocracy. However,... more Expectations of fair competition underlie the assumption that academia is a meritocracy. However, bias may reinforce gender inequality in peer review processes, unfairly eliminating outstanding individuals. Here, we ask whether applicant gender biases peer review in a country top ranked for gender equality. We analyzed peer review assessments for recruitment grants at a Swedish medical university, Karolinska Institutet (KI), during four consecutive years (2014-2017) for Assistant Professor (n = 207) and Senior Researcher (n = 153). We derived a composite bibliometric score to quantify applicant productivity and compared this score with subjective external (non-KI) peer reviewer scores of applicants' merits to test their association for men and women, separately. To determine whether there was gender segregation in research fields, we analyzed publication list MeSH terms, for men and women, and analyzed their overlap. There was no gendered MeSH topic segregation, yet men and women with equal merits are scored unequally by reviewers. Men receive external reviewer scores resulting in stronger associations (steeper slopes) between computed productivity and subjective external reviewer scores, meaning that peer reviewers "reward" men's productivity with proportional merit scores. However, women applying for assistant professor or senior researcher receive only 32 or 92% of the score men receive, respectively, for each additional composite bibliometric score point. As productivity increases, the differences in merit scores between men and women increases. Accumulating gender bias is thus quantifiable and impacts the highest tier of competition, the pool from which successful candidates are ultimately chosen. Track record can be computed, and granting organizations could therefore implement a computed track record as quality control to assess whether bias affects reviewer assessments.

Cell Metabolism, Jun 1, 2014

We previously demonstrated that the deletion of the poly(ADP-ribose)polymerase (Parp)-1 gene in m... more We previously demonstrated that the deletion of the poly(ADP-ribose)polymerase (Parp)-1 gene in mice enhances oxidative metabolism, thereby protecting against diet-induced obesity. However, the therapeutic use of PARP inhibitors to enhance mitochondrial function remains to be explored. Here, we show tight negative correlation between Parp-1 expression and energy expenditure in heterogeneous mouse populations, indicating that variations in PARP-1 activity have an impact on metabolic homeostasis. Notably, these genetic correlations can be translated into pharmacological applications. Long-term treatment with PARP inhibitors enhances fitness in mice by increasing the abundance of mitochondrial respiratory complexes and boosting mitochondrial respiratory capacity. Furthermore, PARP inhibitors reverse mitochondrial defects in primary myotubes of obese humans and attenuate genetic defects of mitochondrial metabolism in human fibroblasts and C. elegans. Overall, our work validates in worm, mouse, and human models that PARP inhibition may be used to treat both genetic and acquired muscle dysfunction linked to defective mitochondrial function.

Signal Transduction and Targeted Therapy, Aug 16, 2023

Biochemistry and Molecular Biology Education

Graduate programs in medicine and biomedical sciences have been severely impacted by the SARS‐CoV... more Graduate programs in medicine and biomedical sciences have been severely impacted by the SARS‐CoV‐2/COVID‐19 pandemic over the last 2 years. Following 2 years since beginning of the pandemic, data on student support, educational and academic performance as well as sentiment on changes to educational programs are starting to emerge. We performed and compared results of two cross‐sectional surveys of Swedish and U.S.‐based medical and biomedical graduate students on how the pandemic has affected their studies, research productivity and career trajectory. Students were also asked to assess support provided by the university and supervisors. The surveys also captured student demographics and a range of other factors, such as pressures brought on by caretaking and financial responsibilities. We analyzed answers from 264 and 106 students attending graduate programs in universities in Sweden and the United States, respectively. U.S.‐based students faced more severe restrictions on their re...

Current Opinion in Genetics & Development

Frontiers in Cell and Developmental Biology

The prevalence of obesity and metabolic diseases continues to rise, which has led to an increased... more The prevalence of obesity and metabolic diseases continues to rise, which has led to an increased interest in studying adipose tissue to elucidate underlying disease mechanisms. The use of genetic mouse models has been critical for understanding the role of specific genes for adipose tissue function and the tissue’s impact on other organs. However, mouse adipose tissue displays key differences to human fat, which has led, in some cases, to the emergence of some confounding concepts in the adipose field. Such differences include the depot-specific characteristics of visceral and subcutaneous fat, and divergences in thermogenic fat phenotype between the species. Adipose tissue characteristics may therefore not always be directly compared between species, which is important to consider when setting up new studies or interpreting results. This mini review outlines our current knowledge about the cell biological differences between human and mouse adipocytes and fat depots, highlighting ...

Obesity Reviews, 2021

SummaryThe prevalence of obesity and its associated pathologies continue to increase, which has l... more SummaryThe prevalence of obesity and its associated pathologies continue to increase, which has led to a renewed interest in our major weight‐regulating organ, the white adipose tissue. It has become clear that its development, expansion, and physiological function depend on proper crosstalk between each of its cellular constituents, with a central role for the vascular endothelium lining the blood vessels. Although first considered a mere barrier, the endothelium has emerged as a dynamic unit modulating many critical adipose tissue functions. It not only oversees the uptake of all nutrients to be stored in the adipocytes but also provides an important growth niche for adipocyte progenitors and regulates the expandability of the tissue during overfeeding and obesity. In this review, we describe the reciprocal relationship between endothelial cells, adipocytes, and obesity. We present recent studies that support an important role for endothelial cells as central mediators of many of ...

International Journal of Molecular Sciences, 2022

Obesity is associated with extensive expansion and remodeling of the adipose tissue architecture,... more Obesity is associated with extensive expansion and remodeling of the adipose tissue architecture, including its microenvironment and extracellular matrix (ECM). Although obesity has been reported to induce adipose tissue fibrosis, the composition of the ECM under healthy physiological conditions has remained underexplored and debated. Here, we used a combination of three established techniques (picrosirius red staining, a colorimetric hydroxyproline assay, and sensitive gene expression measurements) to evaluate the status of the ECM in metabolically healthy lean (MHL) and metabolically unhealthy obese (MUO) subjects. We investigated ECM deposition in the two major human adipose tissues, namely the omental and subcutaneous depots. Biopsies were obtained from the same anatomic region of respective individuals. We found robust ECM deposition in MHL subjects, which correlated with high expression of collagens and enzymes involved in ECM remodeling. In contrast, MUO individuals showed lo...

Frontiers in Research Metrics and Analytics, 2021

Biochemical and Biophysical Research Communications, 2006

Treatments against influenza A viruses (IAV) have to be updated regularly due to antigenic drift ... more Treatments against influenza A viruses (IAV) have to be updated regularly due to antigenic drift and drug resistance. Poly (ADPribose) polymerases (PARPs) are considered effective therapeutic targets of acute lung inflammatory injury. This study aimed to explore the effects of PARP-1 inhibitor olaparib on IAV-induced lung injury and the underlying mechanisms. Male wild-type C57BL/6 mice were intranasally infected with IAV strain H1N1 to mimic pneumonia experimentally. Olaparib at different doses was intraperitoneally injected 2 days before and 5 consecutive days after virus stimulation. On day 6 post-infection, lung tissues as well as bronchoalveolar lavage fluid (BALF) were sampled for histological and biochemical analyses. Olaparib increased the survival rate of IAV mice dose-dependently. Olaparib remarkably reduced IAV mRNA expression, myeloperoxidase (MPO) level, and inflammatory cell infiltration in IAV lungs. Moreover, olaparib significantly reduced the level of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-6, and IL-4 and increased IL-10 in IAV lungs. Also, olaparib efficiently reduced IL-6, monocyte chemotactic protein (MCP)-1, granulocyte colony-stimulating factor (G-CSF), TNF-α, chemokine (C-X-C motif) ligand (CXCL)1, CXCL10, chemokine (C-C motif) ligand (CCL)3, and regulated on activation, normal T cell expressed and secreted (RANTES) release in IAV BALF. Olaparib decreased PARylated protein content and p65, IκBα phosphorylation in IAV lung tissues. This study successfully constructed the pneumonia murine model using IAV. Olaparib decreased IAV-induced mortality in mice, lung injury, and cytokine production possibly via modulation of PARP-1/NF-κB axis.

Obesity Reviews, Dec 5, 2021

The prevalence of obesity and its associated pathologies continue to increase, which has led to a... more The prevalence of obesity and its associated pathologies continue to increase, which has led to a renewed interest in our major weight-regulating organ, the white adipose tissue. It has become clear that its development, expansion, and physiological function depend on proper crosstalk between each of its cellular constituents, with a cen