A distribution-centered approach for analyzing human adipocyte size estimates and their association with obesity-related traits and mitochondrial function

Honecker, Julius; Weidlich, Dominik; Heisz, Simone; Lindgren, Cecilia M.; Karampinos, Dimitrios C.; Claussnitzer, Melina; Hauner, Hans

doi:10.1038/s41366-021-00883-6

Cited by 22 publications

(26 citation statements)

References 52 publications

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“…Obesity is a condition where excess body fat accumulates either due to the enlargement of lipids in existing adipocytes (hypertrophy), or through an increase in the number of adipocytes (hyperplasia) [ 42 ]. Adipose tissue in the human body functions as an energy storage system, an endocrine gland, and a heat productor (nonshivering thermogenesis) [ 43 ].…”

Section: Ca Vs Obesitymentioning

confidence: 99%

Caffeic Acid on Metabolic Syndrome: A Review

et al. 2021

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Metabolic syndrome (MetS) is a constellation of risk factors that may lead to a more sinister disease. Raised blood pressure, dyslipidemia in the form of elevated triglycerides and lowered high-density lipoprotein cholesterol, raised fasting glucose, and central obesity are the risk factors that could lead to full-blown diabetes, heart disease, and many others. With increasing sedentary lifestyles, coupled with the current COVID-19 pandemic, the numbers of people affected with MetS will be expected to grow in the coming years. While keeping these factors checked with the polypharmacy available currently, there is no single strategy that can halt or minimize the effect of MetS to patients. This opens the door for a more natural way of controlling the disease. Caffeic acid (CA) is a phytonutrient belonging to the flavonoids that can be found in abundance in plants, fruits, and vegetables. CA possesses a wide range of beneficial properties from antioxidant, immunomodulatory, antimicrobial, neuroprotective, antianxiolytic, antiproliferative, and anti-inflammatory activities. This review discusses the current discovery of the effect of CA against MetS.

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Section: Ca Vs Obesitymentioning

confidence: 99%

Caffeic Acid on Metabolic Syndrome: A Review

et al. 2021

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“…Measurements of adipocyte number, size and diameter in the dWAT layer were performed on PLIN1-stained skin sections ( n = 3 mice per group), using ImageJ software version v1.53k (National Institutes of Health, Bethesda, MD, USA), as described previously [ 9 ]. To measure the adipocyte size, two methods were applied: (1) the measurement of adipocyte size as a cell area (volume) and (2) feret diameter as a measure of a cell size along a specified direction (the longest distance between any two points restricting the object perpendicular to that direction) [ 53 , 54 ].…”

Section: Methodsmentioning

confidence: 99%

Dermal White Adipose Tissue (dWAT) Is Regulated by Foxn1 and Hif-1α during the Early Phase of Skin Wound Healing

Gawrońska‐Kozak

Walendzik

Machcińska

et al. 2021

IJMS

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Dermal white adipose tissue (dWAT) is involved in the maintenance of skin homeostasis. However, the studies concerning its molecular regulation are limited. In the present paper, we ask whether the introduction of two transcription factors, Foxn1 and Hif-1α, into the post-wounded skin of Foxn1-/- mice regulates dWAT during wound healing (days 3 and 6). We have chosen lentivirus vectors (LVs) as a tool to deliver Foxn1 and Hif-1α into the post-wounded skin. We documented that combinations of both transgenes reduces the number, size and diameter of dermal adipocytes at the wound bed area. The qRT-PCR analysis of pro-adipogenic genes, revealed that LV-Hif-1α alone, or combined with LV-Foxn1, increases the mRNA expression of Pparγ, Glut 4 and Fasn at post-wounding day 6. However, the most spectacular stimulatory effect of Foxn1 and/or Hif-1α was observed for Igf2, the growth factor participating in adipogenic signal transduction. Our data also shows that Foxn1/Hif-1α, at post-wounding day 3, reduces levels of CD68 and MIP-1γ mRNA expression and the percentage of CD68 positive cells in the wound site. In conclusion, the present data are the first to document that Foxn1 and Hif-1α cooperatively (1) regulate dWAT during the proliferative phase of skin wound healing through the Igf2 signaling pathway, and (2) reduce the macrophages content in the wound site.

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“…In addition, a constant term is included in all models, but omitted in the formula for simplicity. The main difference with studies that adjust additively for BMI = BW / height 2 (Glastonbury et al, 2020;Honecker et al, 2021), with models like (cell size~variables + BW / height 2 ) is our interaction term and that our intermediate DW level between cell area and BW. BW and DW were measured with Sartorius BAL7000 scales.…”

Section: Phenotype Framework For Watmentioning

confidence: 99%

“…Healthy white adipocytes may present inter-depot heterogeneity in size, with SAT cells generally larger than VAT (Boumelhem et al, 2017;Fang et al, 2015;Glastonbury et al, 2020); adipocyte diameter is associated with BMI in both depots, but with obesity traits adjusted for BMI only in VAT (Honecker et al, 2021). There is also a sex effect, as females have significantly smaller adipocytes than males in VAT (Glastonbury et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, it is necessary to differentiate between the cells of interest (mature white adipocytes) and other WAT components and image artefacts. For this, tiles can be accepted or rejected as a whole by an InceptionV3 network (Glastonbury et al, 2020;Honecker et al, 2021). This, however, has poor granularity and favours areas away from tissue edges and where other components are less prevalent.…”

Section: Introductionmentioning

confidence: 99%

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Phenotyping of Klf14 mouse white adipose tissue enabled by whole slide segmentation with deep neural networks

Casero

Westerberg

Horner

et al. 2021

Preprint

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White adipose tissue (WAT) plays a central role in metabolism, and multiple diseases and genetic mutations cause its remodeling, most notably obesity, which has reached pandemic levels. WAT is present in subcutaneous (SAT) and visceral (VAT) depots, and its main components are white adipocytes. Quantitative analysis of white adipocyte size and counts is of great interest to understand physiology and disease, due to intra- and inter-depot heterogeneity, as well as better prognosis for hypertrophy than hyperplasia, and for SAT expansion than VAT expansion. H&E histology of whole depot cross-sections provides excellent approximation of cell morphology and preserves spatial information. Previous studies have been limited to window subsampling of whole slides, and cell size analysis. In this paper, we present a deep learning pipeline that can segment overlapping white adipocytes on whole slides and filter out other cells. We also propose a statistical framework based on linear models to study WAT phenotypes with three interconnected levels (body weight BW, depot weight DW and quartile cell area). Applying it to find Klf14 phenotypes in mice using 147 whole slides of WAT H&E histology, we show sexual dimorphism, and different effects between depots, heterozygous parent of origin for the KO allele and genotype (WT vs. Het). In particular, whether variables are correlated (DW vs. BW and cell area vs. DW), and statistical differences between fitted linear models. We also find significant differences between hand-traced or window subsampling datasets and whole slide analysis. Finally, we provide heatmaps of cell size for all the slides, showing substantial spatial heterogeneity and local spatial correlations.

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A distribution-centered approach for analyzing human adipocyte size estimates and their association with obesity-related traits and mitochondrial function

Cited by 22 publications

References 52 publications

Caffeic Acid on Metabolic Syndrome: A Review

Caffeic Acid on Metabolic Syndrome: A Review

Dermal White Adipose Tissue (dWAT) Is Regulated by Foxn1 and Hif-1α during the Early Phase of Skin Wound Healing

Phenotyping of Klf14 mouse white adipose tissue enabled by whole slide segmentation with deep neural networks

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