scholarly journals Differential Effects of Insulin-Deficient Diabetes Mellitus on Visceral vs. Subcutaneous Adipose Tissue—Multi-omics Insights From the Munich MIDY Pig Model

2021 ◽  
Vol 8 ◽  
Author(s):  
Florian Flenkenthaler ◽  
Erik Ländström ◽  
Bachuki Shashikadze ◽  
Mattias Backman ◽  
Andreas Blutke ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
The Body ◽  
Pig Model ◽  
Metabolic Adaptation ◽  
Diabetes Research ◽  
Insulin Deficiency ◽  
Omics Analysis ◽  
Absolute Insulin Deficiency

Adipose tissue (AT) is no longer considered to be responsible for energy storage only but is now recognized as a major endocrine organ that is distributed across different parts of the body and is actively involved in regulatory processes controlling energy homeostasis. Moreover, AT plays a crucial role in the development of metabolic disease such as diabetes. Recent evidence has shown that adipokines have the ability to regulate blood glucose levels and improve metabolic homeostasis. While AT has been studied extensively in the context of type 2 diabetes, less is known about how different AT types are affected by absolute insulin deficiency in type 1 or permanent neonatal diabetes mellitus. Here, we analyzed visceral and subcutaneous AT in a diabetic, insulin-deficient pig model (MIDY) and wild-type (WT) littermate controls by RNA sequencing and quantitative proteomics. Multi-omics analysis indicates a depot-specific dysregulation of crucial metabolic pathways in MIDY AT samples. We identified key proteins involved in glucose uptake and downstream signaling, lipogenesis, lipolysis and β-oxidation to be differentially regulated between visceral and subcutaneous AT in response to insulin deficiency. Proteins related to glycogenolysis, pyruvate metabolism, TCA cycle and lipogenesis were increased in subcutaneous AT, whereas β-oxidation-related proteins were increased in visceral AT from MIDY pigs, pointing at a regionally different metabolic adaptation to master energy stress arising from diminished glucose utilization in MIDY AT. Chronic, absolute insulin deficiency and hyperglycemia revealed fat depot-specific signatures using multi-omics analysis. The generated datasets are a valuable resource for further comparative and translational studies in clinical diabetes research.

scholarly journals Sex Differences in Brown Adipose Tissue Function: Sex Hormones, Glucocorticoids, and Their Crosstalk

2021 ◽  
Vol 12 ◽  
Author(s):  
Kasiphak Kaikaew ◽  
Aldo Grefhorst ◽  
Jenny A. Visser
Keyword(s):  
Sex Differences ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Sex Hormones ◽  
Energy Homeostasis ◽  
Overweight And Obesity ◽  
The Body ◽  
Bat Activity ◽  
Pathological Conditions ◽  
Brown Adipose

Excessive fat accumulation in the body causes overweight and obesity. To date, research has confirmed that there are two types of adipose tissue with opposing functions: lipid-storing white adipose tissue (WAT) and lipid-burning brown adipose tissue (BAT). After the rediscovery of the presence of metabolically active BAT in adults, BAT has received increasing attention especially since activation of BAT is considered a promising way to combat obesity and associated comorbidities. It has become clear that energy homeostasis differs between the sexes, which has a significant impact on the development of pathological conditions such as type 2 diabetes. Sex differences in BAT activity may contribute to this and, therefore, it is important to address the underlying mechanisms that contribute to sex differences in BAT activity. In this review, we discuss the role of sex hormones in the regulation of BAT activity under physiological and some pathological conditions. Given the increasing number of studies suggesting a crosstalk between sex hormones and the hypothalamic-pituitary-adrenal axis in metabolism, we also discuss this crosstalk in relation to sex differences in BAT activity.

Abstract 327: Cardiac Regulation of Metabolic Homeostasis by Med13

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Chad E Grueter ◽  
Kedryn K Baskin ◽  
Christine M Kusminski ◽  
William Holland ◽  
Philipp E Scherer ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Transcriptional Activation ◽  
Energy Homeostasis ◽  
The Body ◽  
Whole Body ◽  
Mediator Complex ◽  
Acid Oxidation ◽  
Dependent Manner ◽  
Metabolite Production ◽  
Body Energy

Alterations in metabolism are a major component of cardiovascular disease associated with obesity and type 2 diabetes. The complex interplay between these three diseases poses a challenge for successful treatment and warrants further studies directed at understanding the intertissue communication between major metabolic organs. We previously identified a signaling pathway within the heart that modulates systemic energy homeostasis by regulation of Med13, a component of the kinase submodule of the Mediator Complex, in the heart. The Mediator Complex is a large, multiprotein complex that functions to integrate signal specific events with transcriptional activation and elongation in a context dependent manner. Our current work further delineates a mechanism by which Med13 in the heart functions to regulate whole body energy homeostasis. The increase in energy expenditure in Med13 transgenic (TG) mice is due in part to increased triglyceride uptake and beta-oxidation in white adipose tissue and liver. Additionally, the expression of Krebs Cycle and fatty acid oxidation genes are increased in adipose tissue and liver as measured by RNA seq and in metabolite production in Med13 Tg mice. Together, these results demonstrate the Mediator Complex regulates cardiac gene expression and metabolite production which communicates with energy depots within the body to modulate whole body energy homeostasis.

scholarly journals The Impact of Single-Cell Genomics on Adipose Tissue Research

2020 ◽  
Vol 21 (13) ◽  
pp. 4773
Author(s):  
Alana Deutsch ◽  
Daorong Feng ◽  
Jeffrey E. Pessin ◽  
Kosaku Shinoda
Keyword(s):  
Adipose Tissue ◽  
Single Cell ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Diabetes Research ◽  
Obesity And Diabetes ◽  
Important Regulator ◽  
Whole Body Metabolism ◽  
Tissue Aging ◽  
The Impact

Adipose tissue is an important regulator of whole-body metabolism and energy homeostasis. The unprecedented growth of obesity and metabolic disease worldwide has required paralleled advancements in research on this dynamic endocrine organ system. Single-cell RNA sequencing (scRNA-seq), a highly meticulous methodology used to dissect tissue heterogeneity through the transcriptional characterization of individual cells, is responsible for facilitating critical advancements in this area. The unique investigative capabilities achieved by the combination of nanotechnology, molecular biology, and informatics are expanding our understanding of adipose tissue’s composition and compartmentalized functional specialization, which underlie physiologic and pathogenic states, including adaptive thermogenesis, adipose tissue aging, and obesity. In this review, we will summarize the use of scRNA-seq and single-nuclei RNA-seq (snRNA-seq) in adipocyte biology and their applications to obesity and diabetes research in the hopes of increasing awareness of the capabilities of this technology and acting as a catalyst for its expanded use in further investigation.

scholarly journals Endocrine Regulation of Energy Metabolism: Review of Pathobiochemical and Clinical Chemical Aspects of Leptin, Ghrelin, Adiponectin, and Resistin

2004 ◽  
Vol 50 (9) ◽  
pp. 1511-1525 ◽  
Author(s):  
Ursula Meier ◽  
Axel M Gressner
Keyword(s):  
Adipose Tissue ◽  
Energy Metabolism ◽  
Energy Homeostasis ◽  
Clinical Chemistry ◽  
The Body ◽  
Storage Site ◽  
Endocrine Regulation ◽  
Highly Active ◽  
Glucose And Lipid Metabolism ◽  
Organ Systems

Abstract Background: Recent studies point to the adipose tissue as a highly active endocrine organ secreting a range of hormones. Leptin, ghrelin, adiponectin, and resistin are considered to take part in the regulation of energy metabolism. Approach: This review summarizes recent knowledge on leptin and its receptor and on ghrelin, adiponectin, and resistin, and emphasizes their roles in pathobiochemistry and clinical chemistry. Content: Leptin, adiponectin, and resistin are produced by the adipose tissue. The protein leptin, a satiety hormone, regulates appetite and energy balance of the body. Adiponectin could suppress the development of atherosclerosis and liver fibrosis and might play a role as an antiinflammatory hormone. Increased resistin concentrations might cause insulin resistance and thus could link obesity with type II diabetes. Ghrelin is produced in the stomach. In addition to its role in long-term regulation of energy metabolism, it is involved in the short-term regulation of feeding. These hormones have important roles in energy homeostasis, glucose and lipid metabolism, reproduction, cardiovascular function, and immunity. They directly influence other organ systems, including the brain, liver, and skeletal muscle, and are significantly regulated by nutritional status. This newly discovered secretory function has extended the biological relevance of adipose tissue, which is no longer considered as only an energy storage site. Summary: The functional roles, structures, synthesis, analytical aspects, and clinical significance of leptin, ghrelin, adiponectin, and resistin are summarized.

Getting the message across: mechanisms of physiological cross talk by adipose tissue

2009 ◽  
Vol 296 (6) ◽  
pp. E1210-E1229 ◽  
Author(s):  
Do-Eun Lee ◽  
Sylvia Kehlenbrink ◽  
Hanna Lee ◽  
Meredith Hawkins ◽  
John S. Yudkin
Keyword(s):  
Adipose Tissue ◽  
Cross Talk ◽  
Energy Homeostasis ◽  
Cellular Level ◽  
The Body ◽  
Low Grade ◽  
Storage Site ◽  
Integrative Physiology ◽  
Energy Excess ◽  
Low Grade Inflammation

Obesity is associated with resistance of skeletal muscle to insulin-mediated glucose uptake, as well as resistance of different organs and tissues to other metabolic and vascular actions of insulin. In addition, the body is exquisitely sensitive to nutrient imbalance, with energy excess or a high-fat diet rapidly increasing insulin resistance, even before noticeable changes occur in fat mass. There is a growing acceptance of the fact that, as well as acting as a storage site for surplus energy, adipose tissue is an important source of signals relevant to, inter alia, energy homeostasis, fertility, and bone turnover. It has also been widely recognized that obesity is a state of low-grade inflammation, with adipose tissue generating substantial quantities of proinflammatory molecules. At a cellular level, the understanding of the signaling pathways responsible for such alterations has been intensively investigated. What is less clear, however, is how alterations of physiology, and of signaling, within one cell or one tissue are communicated to other parts of the body. The concepts of cell signals being disseminated systemically through a circulating “endocrine” signal have been complemented by the view that local signaling may similarly occur through autocrine or paracrine mechanisms. Yet, while much elegant work has focused on the alterations in signaling that are found in obesity or energy excess, there has been less attention paid to ways in which such signals may propagate to remote organs. This review of the integrative physiology of obesity critically appraises the data and outlines a series of hypotheses as to how interorgan cross talk takes place. The hypotheses presented include the “fatty acid hypothesis,”, the “portal hypothesis,”, the “endocrine hypothesis,”, the “inflammatory hypothesis,”, the “overflow hypothesis,”, a novel “vasocrine hypothesis,” and a “neural hypothesis,” and the strengths and weaknesses of each hypothesis are discussed.

scholarly journals Anthropological Characteristic of the Distribution of Adipose Tissue in Bulgarian Females with Type 2 Diabetes Mellitus

Folia Medica ◽  
2018 ◽  
Vol 60 (3) ◽  
pp. 411-416
Author(s):  
Atanas G. Baltadjiev ◽  
Stefka V. Vladeva ◽  
Dimitar B. Bahariev
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Body Fat ◽  
Fat Mass ◽  
Subcutaneous Fat ◽  
The Body ◽  
Fat Tissue

Abstract Background: The complex study of adipose tissue in women with type 2 diabetes mellitus (T2DM) is of importance for the clinical course and prognosis of the disease. Aim: To study the distribution of adipose tissue in Bulgarian females with T2DM. Patients and methods: The study included 92 women with T2DM (age range 40-60 years). The control group consisted of 40 age-matched women. Measurement parameters: height, weight, 9 skinfolds (sf) – sfTriceps, sfBiceps brachii, sfForearm, sfSubscapular, sfXrib, sfAbdomen, sfSuprailiaca, sfThigh, and sfCalf; bioelectrical impedance analysis - % body fat tissue and visceral fat tissue. Calculated indexes: body mass index (BMI), the ratio sfTrunk to sfLimbs, the ratio skin folds upper half of body/skin folds lower half of body, fat mass and subcutaneous fat mass. Results: Statistically significant differences were found in the means of sfTriceps, sfXrib, sfThigh, sfCalf, % body fat tissue, visceral fat tissue, and fat mass and subcutaneous fat mass between the diabetic and healthy women. The body composition of diabetic females aged 40-60 years contained a larger adipose component than controls. Visceral adipose tissue which determines the body composition is a reliable indicator of the health risks in diabetic women. Conclusion: The pattern of subcutaneous adipose tissue distribution in diabetic females aged 40-60 yrs was primarily in the upper torso region and less so in the limbs. In the controls adipose tissue is accumulated primarily in the limbs and in the lower part of the body.

scholarly journals The effect of vitamin E on the development of nephropathy in rabbits with dithizone diabetes

2000 ◽  
Vol 46 (6) ◽  
pp. 41-44
Author(s):  
V. V. Poltorak ◽  
N. I. Gorbenko ◽  
A. I. Gladkikh ◽  
O. V. Ivanova
Keyword(s):  
Diabetes Mellitus ◽  
Vitamin E ◽  
Early Stage ◽  
Insulin Dependent Diabetes Mellitus ◽  
Diabetic Control ◽  
Dependent Diabetes Mellitus ◽  
Insulin Deficiency ◽  
Patients With Diabetes ◽  
Insulin Dependent ◽  
Absolute Insulin Deficiency

The effects of vitamin E (VE) on early-stage diabetic nephropathy were studied in experimental insulin-dependent diabetes mellitus. Absolute insulin deficiency was modelled with an intravenous injection of ditisone to male rabbits (35 mg/kg). Vitamin E (tocoferoli acetatas) was given orally as gelatin capsules, 100 mg per animal daily for 2 months. VE-fed rabbits exhibited a significant lowering of basal hyperglycemia, rise of basal insulinemia, and better glucose tolerance than diabetic control. VE also normalized ditisone-increased level of cholesterol, beta-lipoproteins and reduced concentrations of dienic conjugates in blood serum of the diabetic animals. Angioprotective effect of VE manifesting in lowering of microalbuminuria, mass of the kidney and thickness of basal glomerular membrane validates the efficiency of VE in prevention or attenuation of clinical nephropathy in patients with diabetes mellitus.

scholarly journals The Parathyroid Hormone-Related Protein/Parathyroid Hormone 1 Receptor Axis in Adipose Tissue

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1570
Author(s):  
Adriana Izquierdo-Lahuerta
Keyword(s):  
Diabetes Mellitus ◽  
Adipose Tissue ◽  
Parathyroid Hormone ◽  
Tissue Expansion ◽  
The Body ◽  
Peroxisome Proliferator ◽  
Main Role ◽  
Related Protein ◽  
Peroxisome Proliferator Activated Receptor ◽  
Parathyroid Hormone Related Protein

Adipose tissue is an organ that shows great plasticity and is able to adapt to the conditions to which the body is subdued. It participates in the regulation of energetic homeostasis and has endocrine functions. Recent studies have shown how the parathyroid hormone-related protein (PTHrP)/Parathyroid Hormone Receptor 1 (PTH1R) axis participates in the regulation of adipogenesis, opposing the action of Peroxisome proliferator-activated receptor gamma (PPARγ). In addition to this, PTHrP is overexpressed in adipose tissue in situations of wear and tear of the body, favoring browning and lipolysis in this tissue. It is also overexpressed in adipose tissue in stressful situations but in the opposite direction, in obesity, metabolic syndrome, type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM). In conclusion, the PTHrP/PTH1R axis has a main role in adipose tissue, participating in its differentiation and remodeling. PTHrP might be used in obesity treatment and its complications for its ability to reprogram adipogenesis and adipose tissue expansion, WAT browning and for the improvement of the insulin sensitivity. In addition, PTHrP could even be used as a marker of placental status and maternal adaptations to prevent future metabolic problems in mothers and children, as well as in the treatment of bone-related diseases such as osteoporosis.

Role of maternal nutrition in programming adiposity in the offspring: potential implications of glucocorticoids

2013 ◽  
Vol 14 (1) ◽  
Author(s):  
Christophe Breton
Keyword(s):  
Adipose Tissue ◽  
Birth Weight ◽  
Energy Homeostasis ◽  
Maternal Obesity ◽  
Maternal Nutrition ◽  
The Body ◽  
High Birth Weight ◽  
Storage Unit ◽  
Maternal Undernutrition ◽  
Increased Risk

AbstractThe epidemiological studies initially indicated that maternal undernutrition leading to a low birth weight may predispose to the long-lasting energy balance disorders. A high birth weight due to maternal obesity or diabetes, inappropriate early postnatal nutrition, and rapid catch-up growth, may also sensitize to an increased risk of obesity. As stated by the developmental origin of health and disease concept, the perinatal perturbation of the fetus/neonate nutrient supply might be a crucial determinant of the individual programming of the body weight set point. The adipose tissue is considered as the main fuel storage unit involved in the maintenance of the energy homeostasis. Several models have demonstrated that this tissue is a prime target of the developmental programming in a gender- and depot-specific manner. In the rodents, the perinatal period of life corresponds largely to the period of adipogenesis. In contrast, this phenomenon essentially takes place before birth in bigger mammals. Despite these different developmental time windows, the altricial and precocial species share several common offspring programming mechanisms. Thus, the adipose tissue of the offspring from malnourished dams exhibited impaired glucose uptake and leptin/insulin resistance with increased proinflammatory markers. It also displayed a modified sympathetic activity, circadian rhythm, fatty acid composition, and thermogenesis. This might lead to the reprogrammed metabolism and distribution of the adipose tissue with enhanced adipogenesis and fat accumulation predisposing to adiposity. The inappropriate glucocorticoid (GC) levels and modified tissue sensitivity might be key actors of perinatal programming and long-lasting altered adipose tissue activity in the offspring. Following maternal malnutrition, the epigenetic mechanisms might also be responsible for the adipose tissue programming.

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