scholarly journals Adipose tissue: from amorphous filler to metabolic mastermind

2021 ◽  
Author(s):  
Silvia Corvera
Keyword(s):  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Disease Risk ◽  
Appetite Control ◽  
Fat Storage ◽  
Fuel Distribution ◽  
Adipose Tissue Depots ◽  
Increased Risk ◽  
Adipocyte Hypertrophy ◽  
Adipocyte Hyperplasia

Adipose tissue plays a central role in the control of systemic glucose homeostasis through two major mechanisms: fat storage and secretion of specific cytokines known as adipokines. Fat storage in adipose tissue is critically important, as it prevents lipid deposition in liver and muscle, which in turn results in insulin resistance and increased risk of type 2 diabetes. Secretion of adipokines, such as leptin, protects from fuel depletion through appetite control, and other adipokines control fuel distribution and utilization. Fat storage capacity of adipose tissue increases through two mechanisms, adipocyte hypertrophy and adipocyte hyperplasia. Adipose tissue depots expand differently in diverse individuals and confer varying degrees of metabolic disease risk. There are multiple adipocyte subtypes that together mediate the functions of adipose tissue. They do so through specialized functions such as thermogenesis, which burns fuel to maintain core temperature, and through selective secretion of different adipokines. Much progress has been made in understanding the mechanisms by which adipose tissue controls systemic metabolism, increasing our hope of developing new, effective therapies for metabolic diseases.

scholarly journals Role of Kallikrein 7 in Body Weight and Fat Mass Regulation

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 131
Author(s):  
Anne Kunath ◽  
Juliane Weiner ◽  
Kerstin Krause ◽  
Maren Rehders ◽  
Anastasija Pejkovska ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Fat Mass ◽  
Metabolic Diseases ◽  
Whole Body ◽  
Protective Effects ◽  
Adipocyte Hypertrophy ◽  
Altered Thyroid ◽  
Adipocyte Hyperplasia

Increased plasma and adipose tissue protease activity is observed in patients with type 2 diabetes and obesity. It has been proposed that specific proteases contribute to the link between obesity, adipose tissue inflammation and metabolic diseases. We have recently shown that ablation of the serine protease kallikrein-related peptidase 7 (Klk7) specifically in adipose tissue preserves systemic insulin sensitivity and protects mice from obesity-related AT inflammation. Here, we investigated whether whole body Klk7 knockout (Klk7−/−) mice develop a phenotype distinct from that caused by reduced Klk7 expression in adipose tissue. Compared to littermate controls, Klk7−/− mice gain less body weight and fat mass both under chow and high fat diet (HFD) feeding, are hyper-responsive to exogenous insulin and exhibit preserved adipose tissue function due to adipocyte hyperplasia and lower inflammation. Klk7−/− mice exhibit increased adipose tissue thermogenesis, which is not related to altered thyroid function. These data strengthen our recently proposed role of Klk7 in the regulation of body weight, energy metabolism, and obesity-associated adipose tissue dysfunction. The protective effects of Klk7 deficiency in obesity are likely linked to a significant limitation of adipocyte hypertrophy. In conclusion, our data indicate potential application of specific KLK7 inhibitors to regulate KLK7 activity in the development of obesity and counteract obesity-associated inflammation and metabolic diseases.

scholarly journals Deciphering White Adipose Tissue Heterogeneity

Biology ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 23 ◽  
Author(s):  
Quyen Luong ◽  
Jun Huang ◽  
Kevin Y. Lee
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Lineage Tracing ◽  
The Body ◽  
Functional Heterogeneity ◽  
Tissue Heterogeneity ◽  
Adipose Tissue Depots ◽  
White Adipocytes ◽  
Increased Risk ◽  
Beige Adipocytes

Adipose tissue not only stores energy, but also controls metabolism through secretion of hormones, cytokines, proteins, and microRNAs that affect the function of cells and tissues throughout the body. Adipose tissue is organized into discrete depots throughout the body, and these depots are differentially associated with insulin resistance and increased risk of metabolic disease. In addition to energy-dissipating brown and beige adipocytes, recent lineage tracing studies have demonstrated that individual adipose depots are composed of white adipocytes that are derived from distinct precursor populations, giving rise to distinct subpopulations of energy-storing white adipocytes. In this review, we discuss this developmental and functional heterogeneity of white adipocytes both between and within adipose depots. In particular, we will highlight findings from our recent manuscript in which we find and characterize three major subtypes of white adipocytes. We will discuss these data relating to the differences between subcutaneous and visceral white adipose tissue and in relationship to previous work deciphering adipocyte heterogeneity within adipose tissue depots. Finally, we will discuss the possible implications of adipocyte heterogeneity may have for the understanding of lipodystrophies.

scholarly journals DNA Methylation as a Marker of Body Shape in Premenopausal Women

2021 ◽  
Vol 12 ◽  
Author(s):  
Adeline Divoux ◽  
Alexey Eroshkin ◽  
Edina Erdos ◽  
Katalin Sandor ◽  
Timothy F. Osborne ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Adipose Tissue ◽  
Body Fat ◽  
Body Shape ◽  
Metabolic Diseases ◽  
Premenopausal Women ◽  
Fat Distribution ◽  
The Body ◽  
Fat Depots ◽  
Increased Risk

Preferential accumulation of fat in the gluteo-femoral (GF) depot (pear shape) rather than in the abdominal (A) depot (apple shape), protects against the development of metabolic diseases but the underlying molecular mechanism is still unknown. Recent data, including our work, suggest that differential epigenetic marking is associated with regulation of genes attributed to distinct fat distribution. Here, we aimed to compare the genomic DNA methylation signatures between apple and pear-shaped premenopausal women. To investigate the contribution of upper and lower body fat, we used paired samples of A-FAT and GF-FAT, analyzed on the BeadChip Methylation Array and quantified the differentially methylated sites between the 2 groups of women. We found unique DNA methylation patterns within both fat depots that are significantly different depending on the body fat distribution. Around 60% of the body shape specific DNA methylation sites identified in adipose tissue are maintained ex vivo in cultured preadipocytes. As it has been reported before in other cell types, we found only a hand full of genes showing coordinated differential methylation and expression levels. Finally, we determined that more than 50% of the body shape specific DNA methylation sites could also be detected in whole blood derived DNA. These data reveal a strong DNA methylation program associated with adipose tissue distribution with the possibility that a simple blood test could be used as a predictive diagnostic indicator of young women who are at increased risk for progressing to the apple body shape with a higher risk of developing obesity related complications.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT02728635 and https://clinicaltrials.gov/ct2/show/NCT02226640, identifiers NCT02728635 and NCT02226640.

scholarly journals Relevance of Leptin and Other Adipokines in Obesity-Associated Cardiovascular Risk

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2664 ◽  
Author(s):  
Manuel F. Landecho ◽  
Carlota Tuero ◽  
Víctor Valentí ◽  
Idoia Bilbao ◽  
Magdalena de la Higuera ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Adipose Tissue ◽  
The Body ◽  
Matrix Remodeling ◽  
Nonalcoholic Fatty Liver ◽  
Visceral Fat Accumulation ◽  
Vasoactive Factors ◽  
Increased Risk ◽  
Endocrine Organs ◽  
Adipocyte Hypertrophy

Obesity, which is a worldwide epidemic, confers increased risk for multiple serious conditions including type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Adipose tissue is considered one of the largest endocrine organs in the body as well as an active tissue for cellular reactions and metabolic homeostasis rather than an inert tissue only for energy storage. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a large number of hormones, cytokines, extracellular matrix proteins, and growth and vasoactive factors, which are collectively called adipokines known to influence a variety of physiological and pathophysiological processes. In the obese state, excessive visceral fat accumulation causes adipose tissue dysfunctionality that strongly contributes to the onset of obesity-related comorbidities. The mechanisms underlying adipose tissue dysfunction include adipocyte hypertrophy and hyperplasia, increased inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. This review describes the relevance of specific adipokines in the obesity-associated cardiovascular disease.

Dysregulation of muscle lipid metabolism in rats selectively bred for low aerobic running capacity

2007 ◽  
Vol 292 (6) ◽  
pp. E1631-E1636 ◽  
Author(s):  
Fiona J. Spargo ◽  
Sean L. McGee ◽  
Nick Dzamko ◽  
Matthew J. Watt ◽  
Bruce E. Kemp ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Metabolic Diseases ◽  
Disease Risk ◽  
High Capacity ◽  
Whole Body ◽  
Nonesterified Fatty Acid ◽  
Endurance Running ◽  
Increased Risk ◽  
Amp Activated Protein Kinase

As substrate for evaluation of metabolic diseases, we developed novel rat models that contrast for endurance exercise capacity. Through two-way artificial selection, we created rodent phenotypes of intrinsically low-capacity runners (LCR) and high-capacity runners (HCR) that also differed markedly for cardiovascular and metabolic disease risk factors. Here, we determined skeletal muscle proteins with putative roles in lipid and carbohydrate metabolism to better understand the mechanisms underlying differences in whole body substrate handling between phenotypes. Animals ( generation 16) differed for endurance running capacity by 295%. LCR animals had higher resting plasma glucose (6.58 ± 0.45 vs. 6.09 ± 0.45 mmol/l), insulin (0.48 ± 0.03 vs. 0.32 ± 0.02 ng/ml), nonesterified fatty acid (0.57 ± 0.14 v 0.35 ± 0.05 mM), and triglyceride (TG; 0.47 ± 0.11 vs. 0.25 ± 0.08 mmol/l) concentrations (all P < 0.05). Muscle TG (72.3 ± 14.7 vs. 38.9 ± 6.2 mmol/kg dry muscle wt; P < 0.05) and diacylglycerol (96 ± 28 vs. 42 ± 8 pmol/mg dry muscle wt; P < 0.05) contents were elevated in LCR vs. HCR rats. Accompanying the greater lipid accretion in LCR was increased fatty acid translocase/CD36 content (1,014 ± 80 vs. 781 ± 70 arbitrary units; P < 0.05) and reduced TG lipase activity (0.158 ± 0.0125 vs. 0.274 ± 0.018 mmol·min−1·kg dry muscle wt−1; P < 0.05). Muscle glycogen, GLUT4 protein, and basal phosphorylation states of AMP-activated protein kinase-α1, AMP-activated protein kinase-α2, and acetyl-CoA carboxylase were similar in LCR and HCR. In conclusion, rats with low intrinsic aerobic capacity demonstrate abnormalities in lipid-handling capacity. These disruptions may, in part, be responsible for the increased risk of metabolic disorders observed in this phenotype.

Cardiac adipose tissue, intra-abdominal adipose tissue, and risk for cardio-metabolic diseases in patients with schizophrenia

2017 ◽  
Vol 41 (S1) ◽  
pp. s833-s833
Author(s):  
J. Ruppert ◽  
D. Hartung ◽  
M. Gutberlet ◽  
M. Westhoff-Bleck ◽  
K. Kahl
Keyword(s):  
Physical Activity ◽  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Smoking Behavior ◽  
Magnetic Resonance Tomography ◽  
Lifestyle Behaviors ◽  
Abdominal Adipose Tissue ◽  
The Metabolic Syndrome

IntroductionSchizophrenia is associated with increased physical morbidity and mortality. In particular, cardio-metabolic diseases are more frequent. Several underlying reasons have been discussed, including adverse lifestyle behaviors, or adverse effects of neuroleptic treatment. However, little is known about changes of cardiac and intra-abdominal adipose tissue, both are risk factors for the development of cardio-metabolic diseases.Objectives/aimsTo compare, cardiac and intra-abdominal adipose tissue between patients with schizophrenia and healthy controls.MethodsTen physically healthy patients with schizophrenia according to DSM-V were included, and compared to healthy control subjects. Cardiac and intra-abdominal adipose tissue was quantified using magnetic resonance tomography. Further factors assessed comprise the metabolic syndrome, physical activity, smoking behavior, and scores for the assessment of cardio-metabolic diseases (FINDRISK score and modified ESC score).ResultsCardiac adipose tissue and intra-abdominal adipose tissue was increased in patients with schizophrenia. Further findings were higher diastolic blood pressure, more smoking, less physical activity, and an increase for diabetes and cardiovascular disease risk according to the modified ESC and FINDRISK score.ConclusionsThe new finding in our study is an increase of cardiac adipose tissue, a risk factor for the development of cardiovascular disorders, in physically healthy patients with schizophrenia. Furthermore, the risk for the development of type-2 diabetes mellitus is increased, indicated by higher amount of intra-abdominal adipose tissue, and the results of the FINDRISK score. We conclude that lifestyle alterations, particularly exercise training that has been shown to reduce cardiac and intra-abdominal adipose tissue, should be recommended in patients with schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

MUSCLE DISUSE AS A PIVOTAL PROBLEM IN SARCOPENIA-RELATED MUSCLE LOSS AND DYSFUNCTION

2016 ◽  
pp. 1-9
Author(s):  
K.E. BELL ◽  
M.T. VON ALLMEN ◽  
M.C. DEVRIES ◽  
S.M. PHILLIPS
Keyword(s):  
Older Adults ◽  
Muscle Mass ◽  
Metabolic Diseases ◽  
Disease Risk ◽  
Bed Rest ◽  
Relative Reduction ◽  
Ambulatory Activity ◽  
Anabolic Resistance ◽  
Muscle Disuse ◽  
Increased Risk

An age-associated loss of muscle mass and strength – sarcopenia – begins at around the fifth decade of life, with mass being lost at ~0.5-1.2% per year and strength at ~3% per year. Sarcopenia can contribute to a variety of negative health outcomes, including an increased risk for falls and fractures, the development of metabolic diseases like type 2 diabetes mellitus, and increase the chance of requiring assisted living. Linear sarcopenic declines in muscle mass and strength are, however, punctuated by transient periods of muscle disuse that can accelerate losses of muscle and strength, which could result in increased risk for the aforementioned conditions. Muscle disuse is recognizable with bed rest or immobilization (for example, due to surgery or acute illness requiring hospitalization); however, recent work has shown that even a relative reduction in ambulation (reduced daily steps) results in significant reductions in muscle mass, strength and possibly an increase in disease risk. Although reduced ambulation is a seemingly “benign” form of disuse, compared to bed rest and immobilization, reports have documented that 2-3 weeks of reduced daily steps may induce: negative changes in body composition, reductions in muscle strength and quality, anabolic resistance, and decrements in glycemic control in older adults. Importantly, periods of reduced ambulation likely occur fairly frequently and appear more difficult to fully recover from, in older adults. Here we explore the consequences of muscle disuse due to reduced ambulatory activity in older adults, with frequent comparisons to established models of disuse: bed rest and immobilization.

“Multiple human adipocyte subtypes and mechanisms of their development”

2019 ◽  
Author(s):  
So Yun Min ◽  
Anand Desai ◽  
Zinger Yang ◽  
Agastya Sharma ◽  
Ryan M.J. Genga ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Adipose Tissue ◽  
Disease Risk ◽  
Human Adipose Tissue ◽  
Transcriptional Repressors ◽  
Mesenchymal Progenitor Cells ◽  
Human Adipocyte ◽  
Adipose Tissue Depots ◽  
Beige Adipocytes ◽  
Low Levels

SUMMARYHuman adipose tissue depots perform numerous diverse physiological functions, and are differentially linked to metabolic disease risk, yet only two major human adipocyte subtypes have been described, white and “brown/brite/beige.” The diversity and lineages of adipocyte classes have been studied in mice using genetic methods that cannot be applied in humans. Here we circumvent this problem by studying the fate of single mesenchymal progenitor cells obtained from human adipose tissue. We report that a minimum of four human adipocyte subtypes can be distinguished by transcriptomic analysis, specialized for functionally distinct processes such as adipokine secretion and thermogenesis. Evidence for the presence of these adipocytes subtypes in adult humans is evidenced by differential expression of key adipokines leptin and adiponectin in isolated mature adipocytes. The human adipocytes most similar to the mouse “brite/beige” adipocytes are enriched in mechanisms that promote iron accumulation and protect from oxidative stress, and are derived from progenitors that express high levels of cytokines such as IL1B, IL8, IL11 and the IL6 family cytokine LIF, and low levels of the transcriptional repressors ID1 and ID3. Our finding of this adipocyte repertoire and its developmental mechanisms provides a high-resolution framework to analyze human adipose tissue architecture and its role in systemic metabolism and metabolic disease.

scholarly journals Obesity, insulin resistance and comorbidities ? Mechanisms of association

2014 ◽  
Vol 58 (6) ◽  
pp. 600-609 ◽  
Author(s):  
Ana Valeria B. Castro ◽  
Cathryn M. Kolka ◽  
Stella P. Kim ◽  
Richard N. Bergman
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Polycystic Ovary ◽  
Bone Fragility ◽  
The Body ◽  
Ectopic Fat ◽  
Increased Risk ◽  
Fat Liver

Overall excess of fat, usually defined by the body mass index, is associated with metabolic (e.g. glucose intolerance, type 2 diabetes mellitus (T2DM), dyslipidemia) and non-metabolic disorders (e.g. neoplasias, polycystic ovary syndrome, non-alcoholic fat liver disease, glomerulopathy, bone fragility etc.). However, more than its total amount, the distribution of adipose tissue throughout the body is a better predictor of the risk to the development of those disorders. Fat accumulation in the abdominal area and in non-adipose tissue (ectopic fat), for example, is associated with increased risk to develop metabolic and non-metabolic derangements. On the other hand, observations suggest that individuals who present peripheral adiposity, characterized by large hip and thigh circumferences, have better glucose tolerance, reduced incidence of T2DM and of metabolic syndrome. Insulin resistance (IR) is one of the main culprits in the association between obesity, particularly visceral, and metabolic as well as non-metabolic diseases. In this review we will highlight the current pathophysiological and molecular mechanisms possibly involved in the link between increased VAT, ectopic fat, IR and comorbidities. We will also provide some insights in the identification of these abnormalities. Arq Bras Endocrinol Metab. 2014;58(6):600-9

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