Team Rachel Fisher

A section of human adipose tissue showing adipocytes and macrophages (coloured brown) sounding individual adipocytes (photo: Maria Kolak).

Research focus

Adipose tissue inflammation


Obese/insulin resistant adipose tissue is dysfunctional and this is believed to promote the development of atherosclerosis. Therefore the Fisher team uses a translational approach to investigate relationships between adipose tissue metabolism, inflammation and cardiovascular risk factors.

Major research focus

While an inflammatory state is a well recognised risk factor for cardiovascular disease, low grade systemic inflammation and insulin resistance also occur together with adipose tissue being a site of inflammation. In adipose tissue of obese and insulin resistant subjects the number of macrophages and the production of inflammatory cytokines is increased, while adiponectin production is decreased. Inflammation within adipose tissue has been shown to promote the development of atherosclerosis in mouse models and to be associated with cardiovascular risk factors in humans. Why macrophages are recruited into adipose tissue is unknown, although a key role for the chemokine CCL2 (monocyte chemoattractant protein 1, MCP-1) and has been demonstrated. Adipocyte hypertrophy, adipocyte death and local hypoxia have all been proposed as stimuli for macrophage infiltration, but the underlying mechanisms remain unclear.

 Research within the team focuses on determining how local ceramide production in human adipose tissue is related to macrophage accumulation, inflammation adipose tissue metabolism, since our data have implicated ceramides in these processes. Additionally, we are interested in differences between adipose tissue located at different sites within the body in terms of inflammation, ceramide metabolism and relationships to cardiovascular risk factors.  By studying different human adipose tissue depots (subcutaneous, intra-thoracic, intra-abdominal and perivascular) we are able to consider the consequences of adipose tissue dysfunction on the development of cardiovascular disease at both the local and systemic levels. We use a range of techniques to achieve these goals, combining molecular genetic, human metabolic and epidemiological approaches.  Furthermore, adipose tissue from a range of patient groups is studied.

Team members

Rachel Fisher PhD, Professor, Team Leader

Louisa Cheung PhD, Post Doctoral Fellow

Joanna Gertow PhD Student

Olivera Werngren Laboratory Assistant

Recent key publications

Effects of chronic rosiglitazone therapy on gene expression in human adipose tissue in vivo in patients with type 2 diabetes.
Kolak M, Yki-Järvinen H, Kannisto K, Tiikkainen M, Hamsten A, Eriksson P, et al
J. Clin. Endocrinol. Metab. 2007 Feb;92(2):720-4

Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity.
Kolak M, Westerbacka J, Velagapudi V, Wågsäter D, Yetukuri L, Makkonen J, et al
Diabetes 2007 Aug;56(8):1960-8

ApoB/apoA-I ratio: an independent predictor of insulin resistance in US non-diabetic subjects.
Sierra-Johnson J, Romero-Corral A, Somers V, Lopez-Jimenez F, Walldius G, Hamsten A, et al
Eur. Heart J. 2007 Nov;28(21):2637-43

Fatty acid desaturases in human adipose tissue: relationships between gene expression, desaturation indexes and insulin resistance.
Sjögren P, Sierra-Johnson J, Gertow K, Rosell M, Vessby B, de Faire U, et al
Diabetologia 2008 Feb;51(2):328-35

Genetic variation in the ADIPOR2 gene is associated with liver fat content and its surrogate markers in three independent cohorts.
Kotronen A, Yki-Järvinen H, Aminoff A, Bergholm R, Pietiläinen K, Westerbacka J, et al
Eur. J. Endocrinol. 2009 Apr;160(4):593-602

Systemic inflammation activates the nuclear factor-kappaB regulatory pathway in adipose tissue.
Ekström M, Halle M, Bjessmo S, Liska J, Kolak M, Fisher R, et al
Am. J. Physiol. Endocrinol. Metab. 2010 Aug;299(2):E234-40

Functional changes in adipose tissue in a randomised controlled trial of physical activity.
Sjögren P, Sierra-Johnson J, Kallings L, Cederholm T, Kolak M, Halldin M, et al
Lipids Health Dis 2012 Jun;11():80

Expression of ceramide-metabolising enzymes in subcutaneous and intra-abdominal human adipose tissue.
Kolak M, Gertow J, Westerbacka J, Summers S, Liska J, Franco-Cereceda A, et al
Lipids Health Dis 2012 Sep;11():115

Human mediastinal adipose tissue displays certain characteristics of brown fat.
Cheung L, Gertow J, Werngren O, Folkersen L, Petrovic N, Nedergaard J, et al
Nutr Diabetes 2013 May;3():e66