Meeting Report

Spotlights on Lipid Science from the 36th FEBS Congress,June 25–30, 2011, Torino, Italy

DOI: 10.1002/ejlt.201100317

In June 2011, Torino, the City of 2006 Olympic Winter

Games, became a ‘‘Biochemical Hot Spot’’ on the occasion

of the 36th Congress of the Federation of European

Biochemical Societies.

The main theme of the Congress was ‘‘Biochemistry for

Tomorrow’s Medicine’’ and about 2000 attendees, from

more than 60 nations all over the world, gathered at

Lingotto, the venue of the meeting.

Although the Congress was not specifically focused on

lipid science, I would like to share with EJLST’s readers some

interesting insights that emerged during the Congress.

The symposium ‘‘Metabolic control and disorders’’

covered some aspects of lipid biology that are relevant either

in physiological conditions and in pathology. The symposium

was divided in two parts, ‘‘Nuclear receptors and lipid metab-

olism’’, and ‘‘Molecular perspectives for diabetes.’’

In the first part, ‘‘Nuclear receptors and lipid metab-

olism,’’ B. Staels (Lille, France) presented his latest work

on tumor suppressor p16INK4a (thereafter, p16), one of the

more recently discovered PPARa target genes. Tumor sup-

pressor p16 plays a role in tumors, senescence, aging. A few

years ago B. Staels and his group at Institut Pasteur de Lille

contributed to unravel the multiple roles of p16 by discov-

ering that this protein is induced by PPARa and is responsible

for the inhibition of smooth muscle cell proliferation and

neointima formation following PPARa activation [1].

PPARs, like other nuclear receptors, are deeply involved in

the molecular mechanisms underlying inflammation,

immune response, and those diseases such as cardiovascular

disease and diabetes in which lipid abnormalities are associ-

ated to inflammation. The connections among PPAR signal-

ing, lipid homeostasis and inflammatory response have been

extensively investigated in macrophages, master cells

involved either in the inflammatory response and in athero-

sclerosis. Notably, macrophages are heterogeneous cells and

at least two subtypes exist, M1 macrophages, exhibiting more

pronounced proinflammatory functions (release of proin-

flammatory cytokines and reactive oxygen species), and

M2 macrophages, involved in resolution of inflammation.

The switch between the two subtypes is known as ‘‘macro-

phage polarization.’’ Which are the roles of PPARs and p16 in

this context? Recently, B. Staels and his group added import-

ant pieces to this complex scenario showing that, although

not essential for macrophage maturation, p16 is induced

during their differentiation. More importantly, they showed

that the deficiency of p16 modulates macrophage phenotype

causing a gene expression profile that resembles that found in

Interleukin 4-polarized macrophages and makes them less

pro-inflammatory [2]. These findings may help us better

understand the complexity of inflammatory pathways and

related diseases and how they can be modulated, also by

targeting nuclear receptors.

S. Mandrup (Odense, Denmark) addressed another

important aspect linking nuclear receptors and lipid metab-

olism in her lecture entitled ‘‘The transcriptional network of

PPARg in adipocyte development and function.’’ The

requirement of PPARg for adipocyte differentiation is a

widely accepted concept, however, the fine dynamics and

genome-wide actions of this nuclear receptor in differentiat-

ing cells are still elusive. In recent years S. Mandrup and her

coworkers at the University of Southern Denmark have

studied the dynamics of the association of PPARg to chro-

matin (in technical terms ‘‘occupancy’’) and chromatin

remodeling, at the genome-wide level, by applying up-to-date

techniques such as Chromatin Immunoprecipitation

sequencing and deep sequencing. By these means, S.

Mandrup obtained a genome-wide map of PPARg target

sites and a global map of the occupancy of RNA

Polymerase II (the master enzyme in gene transcription)

during differentiation of adipocytes. Moreover, the occu-

pancy of these sites varies during adipogenesis suggesting

that the process of differentiation is associated to temporally

dynamic marking (i.e., the ‘‘sitting’’ of transcription factors

and other regulators on specific spots) of chromatin [3]. To

further investigate chromatin remodeling in differentiating

adipocytes, S. Mandrup applied the technology of deep

sequencing to map hotspots, i.e., chromatin regions that

are less compacted and therefore more susceptible to

DNase I digestion [4]. Collectively, these studies allow to

gain valuable insights on the cooperation among transcription

factors at specific chromatin sites, the coordinated regulation

of transcription of previously unrelated genes, and the

importance of genome dynamics in basic cellular processes

such as differentiation.

Among the selected abstracts, N. Mitro (Milan, Italy)

presented published [5] and unpublished data on the links

between lipid metabolism and neuropathy in a diabetic set-

ting. He showed that administration of a synthetic LXR

ligand to diabetic rats specifically increases the expression

of genes involved in cholesterol, steroid, and fatty acid metab-

olism, and restores steroid and fatty acid levels in peripheral

nerves. In addition, these biochemical changes are associated

1420 Eur. J. Lipid Sci. Technol. 2011, 113, 1420–1422

� 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.ejlst.com

to improvement of some morphological features of myelin

and recovery from peripheral neuropathy.

J. Auwerx (Lausanne, Switzerland) opened the

Symposium ‘‘Molecular perspectives for diabetes’’ with

a stimulating and updated overview on the control of energy

metabolism entitled ‘‘Transcriptional cofactors and NADþ in

the control of metabolism.’’ Although, at a first glance, this

topic does not seem to be directly related to lipid science, the

control of energy metabolism is intimately linked to fatty acid

utilization and storage and, consequently, to metabolic dis-

orders such as diabetes and obesity. The NADþ/NADH

couple primarily drives oxidation reactions and their ratio

reflects the energy status of cells and tissues. A more complete

understanding of NADþ biochemical roles emerged with the

discovery of sirtuins, NADþ consuming enzymes and sensors/

regulators of energy metabolism. J. Auwerx presented his

most recent data that link NADþ-producing and -consuming

pathways to transcriptional networks involving SIRT1, and

the transcriptional coactivators GCN5 and PGC-1a [6, 7].

These studies, combining genetically engineered animal

models and pharmacological tools, clearly suggest that modu-

lation of NADþ levels may be an innovative approach for the

prevention and treatment of metabolic diseases.

Energy metabolism is crucial for proper heart function. In

this context, A. Dobrzyn (Warsaw, Poland) presented her

recent work on the effects of stearoyl-CoA desaturase

deficiency and fatty acid feeding on cardiac metabolism

and function. Based on the observation that obese leptin-

deficient mice display left ventricular hypertrophy associated

with triglyceride accumulation and increased stearoyl-CoA

desaturase activity in cardiomyocytes, A. Dobrzyn

thoroughly investigated the effects of stearoyl-CoA desatur-

ase gene disruption. She found that cardiac functions are

improved in obese mice lacking stearoyl-CoA desaturase,

and notably, these changes are associated with restoration

of biochemical functions, i.e., reduced b-oxidation and

accumulation of fatty acids in cardiomyocytes [8]. These

results suggest that the expression of stearoyl-CoA desaturase

and/or endogenously synthesized oleic acid plays an import-

ant role in the regulation of cardiac substrate utilization. In

line with this hypothesis she demonstrated that oleate, deriv-

ing either from the diet or from de novo biosynthesis through

the action of stearoyl-CoA desaturase, shifts substrate utiliz-

ation toward fatty acids and reduces glucose metabolism in

cardiomyocytes of wild type mice [9].

M. Crestani (Milan, Italy), presenting one of the

selected abstracts, provided experimental evidence that

energy metabolism can be also regulated acting at the level

of histone deacetylases, enzymes that contribute to chromatin

remodeling. By using specific inhibitors in cell cultures and in

a mouse model of diabetes/obesity, M. Crestani and co-

workers demonstrated that inhibition of class I histone deace-

tylase activity results in profound metabolic effects, i.e.,

upregulation of oxidative and mitochondrial genes, and amel-

ioration of the diabetic phenotype.

The links between metabolic diseases and energetics were

also addressed in the symposium ‘‘Redox balance and

obesity.’’ L. Casteilla (Paris, France) focused his presen-

tation on the intriguing hypothesis that mitochondrially

generated reactive oxygen species may act as a physiological

signal that affects adipogenesis and white adipose tissue

functions.

In the symposium ‘‘Networks and circuits,’’ B.

Bakker (Groeningen, The Netherlands) presented an

example of a ‘‘systems biology’’ approach applied to lipid

science and its potential contribution in understanding

whole-body functions and dysfunctions. B. Bakker discussed

the development of comprehensive and quantitative compu-

tational models of fatty acid metabolism that can predict

metabolic behavior. Based on experimental data, these

models provide valuable predictions regarding the multiple

facets of fatty acid metabolism such as substrate competition,

thermodynamic constraints, metabolite channeling and inter-

play between fatty acid and carbohydrate metabolism.

Unfortunately, it is not possible to summarize all contri-

butions, either oral and poster presentations, dealing with

other aspects of lipid science but I wish to share with EJLST’s

readers some ‘‘messages’’ and general thoughts I ‘‘took-

home’’ from the 36th FEBS Congress: basic research is

indispensable to set the bases of tomorrow’s medicine; up-

to-date technologies and approaches such as genome-wide

and ‘‘omics’’ techniques, systems biology, etc., represent an

extraordinary means to expand our knowledge and should be

further and constantly developed; gathering in meetings and

symposia is a refreshing experience that inspires enthusiasm

and new ideas.

The 37th FEBS Congress will be held in Seville, Spain,

September 4–9, 2012 and the main theme will be ‘‘From

Single Molecules to Systems Biology.’’

Dr. Emma De Fabiani

Department of Pharmacological Sciences,

Universita degli Studi di Milano, Milano Italy

E-mail: emma.defabiani@unimi.it

References

[1] Gizard, F., Amant, C., Barbier, O., Bellosta, S. et al., PPARalpha inhibits vascular smooth muscle cell proliferation under-lying intimal hyperplasia by inducing the tumor suppressorp16INK4a. J. Clin. Invest. 2005, 115, 3228–3238.

[2] Cudejko, C., Wouters, K., Fuentes, L., Hannou, S. A. et al.,p16INK4a deficiency promotes IL-4-induced polarizationand inhibits proinflammatory signaling in macrophages.Blood 2011, 118, 2556–2566.

[3] Nielsen, R., Pedersen, T. A., Hagenbeek, D., Moulos, P.et al., Genome-wide profiling of PPARgamma:RXR andRNA polymerase II occupancy reveals temporal activationof distinct metabolic pathways and changes in RXR dimercomposition during adipogenesis. Genes Dev. 2008, 22, 2953–2967.

Eur. J. Lipid Sci. Technol. 2011, 113, 1420–1422 Meeting report 1421

� 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.ejlst.com

[4] Siersbaek, R., Nielsen, R., John, S., Sung, M. H. et al.,Extensive chromatin remodelling,establishment of transcrip-tion factor ’hotspots’ during early adipogenesis. EMBO J.2011, 30, 1459–1472.

[5] Cermenati, G., Giatti, S., Cavaletti, G., Bianchi, R. et al.,Activation of the liver X receptor increases neuroactive steroidlevels and protects from diabetes-induced peripheral neuro-pathy. J. Neurosci. 2010, 30, 11896–11901.

[6] Bai, P., Canto, C., Brunyanszki, A., Huber, A. et al., PARP-2regulates SIRT1 expression and whole-body energy expendi-ture. Cell Metab. 2011, 13, 450–460.

[7] Bai, P., Canto, C., Oudart, H., Brunyanszki, A. et al., PARP-1inhibition increases mitochondrial metabolism throughSIRT1 activation. Cell Metab. 2011, 13, 461–468.

[8] Dobrzyn, P., Dobrzyn, A., Miyazaki, M., Ntambi, J. M., Lossof stearoyl-CoA desaturase 1 rescues cardiac function inobese leptin-deficient mice. J. Lipid Res. 2010, 51, 2202–2210.

[9] Dobrzyn, P., Pyrkowska, A., Jazurek, M., Dobrzyn, A.,Increased availability of endogenous and dietary oleic acidcontributes to the upregulation of cardiac fatty acid oxidation.Mitochondrion in press. DOI: 10.1016/j.mito.2011.05.007.

1422 E. De Fabiani Eur. J. Lipid Sci. Technol. 2011, 113, 1420–1422

� 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.ejlst.com