Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Diabetologia
Published in: Diabetologia 7/2015

Open Access 01-07-2015 | Article

The limited storage capacity of gonadal adipose tissue directs the development of metabolic disorders in male C57Bl/6J mice

Authors: Lianne van Beek, Jan B. van Klinken, Amanda C. M. Pronk, Andrea D. van Dam, Eline Dirven, Patrick C. N. Rensen, Frits Koning, Ko Willems van Dijk, Vanessa van Harmelen

Published in: Diabetologia | Issue 7/2015

Login to get access

Abstract

Aims/hypothesis

White adipose tissue (WAT) consists of various depots with different adipocyte functionality and immune cell composition. Knowledge of WAT-depot-specific differences in expandability and immune cell influx during the development of obesity is limited, therefore we aimed to characterise different WAT depots during the development of obesity in mice.

Methods

Gonadal WAT (gWAT), subcutaneous WAT (sWAT) and mesenteric WAT (mWAT) were isolated from male C57Bl/6J mice with different body weights (approximately 25–60 g) and analysed. Linear and non-linear regression models were used to describe the extent of WAT depot expandability and immune cell composition as a function of body weight.

Results

Whereas mouse sWAT and mWAT continued to expand with body weight, gWAT expanded mainly during the initial phase of body weight gain. The expansion diminished after the mice reached a body weight of around 40 g. From this point on, gWAT crown-like structure formation, liver steatosis and insulin resistance occurred. Mouse WAT depots showed major differences in immune cell composition: gWAT consisted mainly of macrophages, whereas sWAT and mWAT primarily contained lymphocytes.

Conclusions/interpretation

Marked inter-depot differences exist in WAT immune cell composition and expandability. The limited storage capacity of gWAT seems to direct the development of metabolic disorders in male C57Bl/6J mice.
Appendix
Available only for authorised users
Literature
1.
Lee MJ, Wu Y, Fried SK (2013) Adipose tissue heterogeneity: implication of depot differences in adipose tissue for obesity complications. Mol Asp Med 34:1–11CrossRef
2.
3.
Bjorndal B, Burri L, Staalesen V, Skorve J, Berge RK (2011) Different adipose depots: their role in the development of metabolic syndrome and mitochondrial response to hypolipidemic agents. J Obes 2011:490650PubMedCentralPubMedCrossRef
4.
5.
Xu H, Barnes GT, Yang Q et al (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830PubMedCentralPubMedCrossRef
6.
7.
van Beek L, Lips MA, Visser A et al (2014) Increased systemic and adipose tissue inflammation differentiates obese women with T2DM from obese women with normal glucose tolerance. Metab Clin Exp 63:492–501PubMedCrossRef
8.
Murano I, Barbatelli G, Parisani V et al (2008) Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. J Lipid Res 49:1562–1568PubMedCrossRef
9.
Cinti S, Mitchell G, Barbatelli G et al (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46:2347–2355PubMedCrossRef
10.
Winer DA, Winer S, Shen L et al (2011) B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med 17:610–617PubMedCentralPubMedCrossRef
11.
Wu H, Ghosh S, Perrard XD et al (2007) T cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation 115:1029–1038PubMedCrossRef
12.
Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91PubMedCrossRef
13.
14.
Chau YY, Bandiera R, Serrels A et al (2014) Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source. Nat Cell Biol 16:367–375PubMedCentralPubMedCrossRef
15.
Vatier C, Kadiri S, Muscat A, Chapron C, Capeau J, Antoine B (2012) Visceral and subcutaneous adipose tissue from lean women respond differently to lipopolysaccharide-induced alteration of inflammation and glyceroneogenesis. Nutr Diabetes 2, e51PubMedCentralPubMedCrossRef
16.
Bigornia SJ, Farb MG, Mott MM et al (2012) Relation of depot-specific adipose inflammation to insulin resistance in human obesity. Nutr Diabetes 2, e30PubMedCentralPubMedCrossRef
17.
18.
Vroegrijk IO, van Klinken JB, van Diepen JA et al (2013) CD36 is important for adipocyte recruitment and affects lipolysis. Obesity 21:2037–2045PubMedCrossRef
19.
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808PubMedCentralPubMedCrossRef
20.
Kintscher U, Hartge M, Hess K et al (2008) T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol 28:1304–1310PubMedCrossRef
21.
Nishimura S, Manabe I, Nagasaki M et al (2009) CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 15:914–920PubMedCrossRef
22.
Sackmann-Sala L, Berryman DE, Munn RD, Lubbers ER, Kopchick JJ (2012) Heterogeneity among white adipose tissue depots in male C57BL/6J mice. Obesity 20:101–111PubMedCentralPubMedCrossRef
23.
Marchesini G, Brizi M, Bianchi G et al (2001) Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 50:1844–1850PubMedCrossRef
24.
Strissel KJ, Stancheva Z, Miyoshi H et al (2007) Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes 56:2910–2918PubMedCrossRef
25.
Wang QA, Tao C, Gupta RK, Scherer PE (2013) Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat Med 19:1338–1344PubMedCentralPubMedCrossRef
26.
Joe AW, Yi L, Even Y, Vogl AW, Rossi FM (2009) Depot-specific differences in adipogenic progenitor abundance and proliferative response to high-fat diet. Stem Cells 27:2563–2570PubMedCrossRef
27.
28.
Skurk T, Alberti-Huber C, Herder C, Hauner H (2007) Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 92:1023–1033PubMedCrossRef
29.
Shimotsuma M, Shields JW, Simpson-Morgan MW et al (1993) Morpho-physiological function and role of omental milky spots as omentum-associated lymphoid tissue (OALT) in the peritoneal cavity. Lymphology 26:90–101PubMed
30.
Hosogai N, Fukuhara A, Oshima K et al (2007) Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 56:901–911PubMedCrossRef
31.
Rausch ME, Weisberg S, Vardhana P, Tortoriello DV (2008) Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T cell infiltration. Int J Obes 32:451–463CrossRef
32.
Halberg N, Khan T, Trujillo ME et al (2009) Hypoxia-inducible factor 1alpha induces fibrosis and insulin resistance in white adipose tissue. Mol Cell Biol 29:4467–4483PubMedCentralPubMedCrossRef
33.
Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR (2008) Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 57:3239–3246PubMedCentralPubMedCrossRef
34.
Prieur X, Mok CY, Velagapudi VR et al (2011) Differential lipid partitioning between adipocytes and tissue macrophages modulates macrophage lipotoxicity and M2/M1 polarization in obese mice. Diabetes 60:797–809PubMedCentralPubMedCrossRef
35.
Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277–359PubMedCrossRef
36.
Harms M, Seale P (2013) Brown and beige fat: development, function and therapeutic potential. Nat Med 19:1252–1263PubMedCrossRef
37.
Townsend KL, Tseng YH (2014) Brown fat fuel utilization and thermogenesis. Trends Endocrinol Metab 25:168–177
Metadata
Title
The limited storage capacity of gonadal adipose tissue directs the development of metabolic disorders in male C57Bl/6J mice
Authors
Lianne van Beek
Jan B. van Klinken
Amanda C. M. Pronk
Andrea D. van Dam
Eline Dirven
Patrick C. N. Rensen
Frits Koning
Ko Willems van Dijk
Vanessa van Harmelen
Publication date
01-07-2015
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 7/2015
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-015-3594-8

Other articles of this Issue 7/2015

Diabetologia 7/2015 Go to the issue

Article

Human islet function following 20 years of cryogenic biobanking

Short Communication

Type 2 diabetes mellitus and microvascular complications 1 year after Roux-en-Y gastric bypass: a case–control study

Article

Maternal overweight and obesity are associated with increased risk of type 1 diabetes in offspring of parents without diabetes regardless of ethnicity

Article

Higher glucose, insulin and insulin resistance (HOMA-IR) in childhood predict adverse cardiovascular risk in early adulthood: the Pune Children’s Study

Letter

Comparison of HOMA-IR, HOMA-β% and disposition index between US white men and Japanese men in Japan in the ERA JUMP study: was the calculation of disposition index legitimate? Reply to Yamauchi K, Sato Y, Nakasone Y et al [letter]

Article

Mitochondrial succinate dehydrogenase is involved in stimulus-secretion coupling and endogenous ROS formation in murine beta cells
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits