Markers of Adipogenesis, but Not Inflammation, in Adipose Tissue Are Independently Related to Insulin Sensitivity

Matulewicz, Natalia; Stefanowicz, Magdalena; Nikołajuk, Agnieszka; Karczewska-Kupczewska, Monika

doi:10.1210/jc.2017-00597

Cited by 36 publications

(40 citation statements)

References 35 publications

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“…Blunted expression of these transcriptional factors can impair adipogenesis and insulin sensitivity (Dubois et al, 2006). Matulewicz et al (2017) demonstrated that in a young cohort of overweight and obese individuals, adipose tissue expression of adipogenic markers significantly decreased in comparison to normal-weight individuals. Similarly, in our slightly older subject population we observed reduced expression of PPARγ in adipose tissue-derived MSC, suggesting that MSC share impairments observed in surrounding adipose tissue.…”

Section: Discussionmentioning

confidence: 99%

Human Obesity Induces Dysfunction and Early Senescence in Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells

Conley

Hickson

Kellogg

et al. 2020

Front. Cell Dev. Biol.

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Background: Chronic inflammatory conditions like obesity may adversely impact the biological functions underlying the regenerative potential of mesenchymal stromal/stem cells (MSC). Obesity can impair MSC function by inducing cellular senescence, a growth-arrest program that transitions cells to a pro-inflammatory state. However, the effect of obesity on adipose tissue-derived MSC in human subjects remains unclear. We tested the hypothesis that obesity induces senescence and dysfunction in human MSC. Methods: MSC were harvested from abdominal subcutaneous fat collected from obese and age-matched non-obese subjects (n = 40) during bariatric or kidney donation surgeries, respectively. MSC were characterized, their migration and proliferation assessed, and cellular senescence evaluated by gene expression of cell-cycle arrest and senescence-associated secretory phenotype markers. In vitro studies tested MSC effect on injured human umbilical vein endothelial cells (HUVEC) function. Results: Mean age was 59 ± 8 years, 66% were females. Obese subjects had higher body-mass index (BMI) than non-obese. MSC from obese subjects exhibited lower proliferative capacities than non-obese-MSC, suggesting decreased function, whereas their migration remained unchanged. Senescent cell burden and phenotype, manifested as p16, p53, IL-6, and MCP-1 gene expression, were significantly upregulated in obese subjects' MSC. BMI correlated directly with expression of p16, p21, and IL-6. Furthermore, co-incubation with non-obese, but not with obese-MSC, restored VEGF expression and tube formation that were blunted in injured HUVEC. Conclusion: Human obesity triggers an early senescence program in adipose tissue-derived MSC. Thus, obesity-induced cellular injury may alter efficacy of this endogenous repair system and hamper the feasibility of autologous transplantation in obese individuals.

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Section: Discussionmentioning

confidence: 99%

Human Obesity Induces Dysfunction and Early Senescence in Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells

Conley

Hickson

Kellogg

et al. 2020

Front. Cell Dev. Biol.

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“…The CCAAT/enhancer-binding protein α (CEBPA) gene encodes a transcription factor, containing a basic-leucine zipper domain that recognizes the CCAAT sequence in the promoter region of specific target genes that indirectly participates in the regulation of multiple pathways, including glucose and lipid metabolism [70,71]. In humans, several studies have found a lower expression of CEBPA in obese groups [72,73] despite being usually associated to adipogenesis, adipose tissue development and lipid accumulation [71,74]. However, in our study, CEBPA was found upregulated in the obese AL (log2 FC = 0.974, q < 0.05) supporting the concept of increased lipid synthesis in this breed.…”

Section: Gene Expression Analysis: Deseq2mentioning

confidence: 99%

Comparative Transcriptomic Analysis of Subcutaneous Adipose Tissue from Local Pig Breeds

Albuquerque

Óvilo

Núñez

et al. 2020

Genes

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When compared to modern lean-type breeds, Portuguese local Alentejano (AL) and Bísaro (BI) pig breeds present a high potential for subcutaneous and intramuscular fat (IMF) deposition which contributes for better meat quality. The aim of this work was to explore the genome function to better understand the underlying physiological mechanisms associated with body fat accretion. Dorsal subcutaneous fat samples were collected at slaughter from adult animals (n = 4 for each breed) with~150 kg body weight. Total RNA was obtained and sequenced for transcriptome analysis using DESeq2. A total of 458 differentially expressed (DE) genes (q-value < 0.05) were identified, with 263 overexpressed in AL and 195 in BI. Key genes involved in de novo fatty acid biosynthesis, elongation and desaturation were upregulated in AL such as ACLY, FASN, ME1, ELOVL6 and SCD. A functional enrichment analysis of the DE genes was performed using Ingenuity Pathway Analysis. Cholesterol synthesis is suggested to be higher in AL via SREBF2, SCAP and PPARG, while lipolytic activity may be more active in BI through GH and AMPK signalling. Increased signalling of CD40 together with the predicted activation of INSIG1 and INSIG2 in BI suggests that this breed is more sensitive to insulin whereas the AL is less sensitive like the Iberian breed.Genes 2020, 11, 422 2 of 20 inherent genetic value for biodiversity, local breeds are used to produce high quality dry-cured meat products, representing an important role in local economies, culture and landscape as the basics of sustainable local pork chains [2,4].Alentejano (AL) and Bísaro (BI) are the two main Portuguese pig breeds. AL evolved from the primitive Sus scrofa mediterraneus, belongs to the Mediterranean group of breeds [5] and is genetically similar to the Iberian (IB) pig [6]. This breed is commonly raised in the south of Portugal and generally characterized by its light bone structure, black color, short and slim extremities and energetic nature [7]. A medium-sized pig, the AL grows at a low rate (except under the finishing phase "montanheira") and presents a low prolificacy [8]. On the other hand, its high and early adipogenic activity provides a meat and fat composition that is attractive for both fresh meat market and for processing high-grade sausage and dry cured products [9,10]. Traditionally, the AL pig is raised under extensive conditions in an integrated pastoral system ("montado") and during the fattening season is fed with acorns from the existing Quercus forests from October to February [5,7]. BI breed belongs to the Celtic group [5], sharing ancestors with highly productive breeds such as Large-White and Landrace. Production of BI is distributed throughout the north of Portugal, from the Tagus River to the northern border with Spain. It is characterized by its docile temperament, presenting a large body with large legs, head and shoulders. BI pig presents a higher prolificacy and productivity than AL, though lower than other genotypes with similar origins but raised under intensive ...

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“…Body weight of the participants had remained stable (±1 kg) for at least 3 months prior to the study. Participants underwent clinical examination, anthropometric measurements and appropriate laboratory tests (27,28). All the studies were performed after overnight fast.…”

Section: Study Groupsmentioning

confidence: 99%

“…Insulin sensitivity was measured with the 2 h hyperinsulinemic-euglycemic clamp (27,28). On the morning of the study, two venous catheters were inserted into antecubital veins, one for the infusion of insulin and glucose and the other in the contralateral hand for blood sampling, with that hand heated to ~60°C.…”

Section: Measurement Of Insulin Sensitivitymentioning

confidence: 99%

Changes in adipose tissue lipolysis gene expression and insulin sensitivity after weight loss

Karczewska-Kupczewska

Nikołajuk

Majewski

et al. 2020

Endocrine Connections

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Objective Insulin resistance is a major pathophysiological link between obesity and its metabolic complications. Weight loss (WL) is an effective tool to prevent obesity-related diseases; however, the mechanisms of an improvement in insulin sensitivity (IS) after weight-reducing interventions are not completely understood. The aim of the present study was to analyze the relationships between IS and adipose tissue (AT) expression of the genes involved in the regulation of lipolysis in obese subjects after WL. Methods Fifty-two obese subjects underwent weight-reducing dietary intervention program. The control group comprised 20 normal-weight subjects, examined at baseline only. Hyperinsulinemic-euglycemic clamp and s.c. AT biopsy with subsequent gene expression analysis were performed before and after the program. Results AT expression of genes encoding lipases (PNPLA2, LIPE and MGLL) and lipid-droplet proteins enhancing (ABHD5) and inhibiting lipolysis (PLIN1 and CIDEA) were decreased in obese individuals in comparison with normal-weight individuals. The group of 38 obese participants completed dietary intervention program and clamp studies, which resulted in a significant WL and an improvement in mean IS. However, in nine subjects from this group IS did not improve in response to WL. AT expression of PNPLA2, LIPE and PLIN1 increased only in the group without IS improvement. Conclusions Excessive lipolysis may prevent an improvement in IS during WL. The change in AT PNPLA2 and LIPE expression was a negative predictor of the change in IS after WL.

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Markers of Adipogenesis, but Not Inflammation, in Adipose Tissue Are Independently Related to Insulin Sensitivity

Cited by 36 publications

References 35 publications

Human Obesity Induces Dysfunction and Early Senescence in Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells

Human Obesity Induces Dysfunction and Early Senescence in Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells

Comparative Transcriptomic Analysis of Subcutaneous Adipose Tissue from Local Pig Breeds

Changes in adipose tissue lipolysis gene expression and insulin sensitivity after weight loss

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