Riojas, Adriana

Morales-Marroquín, Flor E.

García-Rivas, Gerardo

García, ⁎Noemí

Elsevier - Publisher Connector 

15P15
The beneﬁcial effects of medium-chain fatty acids on metabolism
and oxidative stress
M.K. Montgomery1, G.J. Maghzal2, R. Stocker2, G.J. Cooney1, N. Turner1
1Diabetes & Obesity Research Program, Garvan Institute of Medical
Research, NSW 2010, Australia
2School of Medical Science, University of Sydney, NSW 2006, Australia
E-mail: m.montgomery@garvan.org.au
Dietary intake of long-chain fatty acids (LCFA, CN16) plays a
causative role in insulin resistance and risk of diabetes. Whereas
LCFA promote lipid accumulation and have detrimental effects on
metabolic health, diets rich in medium-chain fatty acids (MCFA; C8–
C14) have been associated with increased oxidative metabolism and
reduced adiposity, with little effect on insulin action in vivo. The
molecular mechanisms underlying these differences are poorly under-
stood. To shed light into this question, we have treated L6 myotubes
with speciﬁc MCFA (capric acid, 10:0 and lauric acid, 12:0) and LCFA
(palmitic acid, 16:0 and oleic acid, 18:1) and determined the effect of
fatty acid treatment on metabolic parameters including triglyceride
accumulation and insulin-stimulated glycogen synthesis as a measure
of insulin sensitivity. A potential mechanism linking lipid accumulation
and insulin resistance is increased oxidative stress within the insulin-
sensitive tissue. Therefore, these studies were extended by measuring
reactive oxygen species (ROS) production and oxidative damage in
muscle cells treated with different fatty acids.
Incubation of myotubes with LCFA led to lipid accumulation
(+90% with palmitic acid vs. control BSA-treated cells, pb0.01),
impaired glycogen synthesis (−40%, pb0.05) and decreased succi-
nate dehydrogenase activity (−40–55% vs. control, pb0.05), however
these deleterious effects were not observed in the MCFA-treated
myotubes. Furthermore, ROS generation (both superoxide and
hydrogen peroxide), measured using HPLC and spectrophotometry,
was not signiﬁcantly altered with MCFA, but was signiﬁcantly greater
in the LCFA-treated cells (+500% vs. control, pb0.001), suggesting
that MCFA might prevent the induction of oxidative stress. Increased
oxidative stress with LCFA, but not MCFA, was conﬁrmed by
measuring a marker of lipoxidative damage, lipid hydroperoxides,
which were increased by LCFA (+40% vs. control, pb0.01), but
remained unchanged in the MCFA-treated cells.
These results show that treatment of muscle cells with MCFA does
not produce the detrimental metabolic effects observed when cells
are exposed to LCFA. A potential mechanism is the differential effects
observed in ROS production and oxidative damage in the MCFA- and
LCFA-treated L6 myotubes.
doi:10.1016/j.bbabio.2012.06.327
15P16
Obesity generates metabolic alterations in the myocardium
leading to changes in mitochondrial membrane permeability
Adriana Riojas, Flor E. Morales-Marroquín, Gerardo García-Rivas,
⁎Noemí García
Cátedra de Cardiología y Medicina Vascular. Escuela de Medicina y
Ciencias de la Salud, Instituto Tecnológico de Monterrey, Monterrey
Nuevo León, Mexico
E-mail: garcianr@itesm.mx
Obesity is a chronic disease of multifactorial origin, characterized
by an excessive accumulation of fat that generates multiple metabolic
disorders leading to cardiovascular diseases (concentric cardiac
hypertrophy, hypertension, atherosclerosis and heat failure), diabetes
mellitus type 2, among others. High lipid accumulation has been
found in the heart of obese rats and humans1, and in addition it has
been described that the apoptotic signaling pathway is active in
hearts from obese patients2. Apoptotic cell death involves several
mechanisms; one of them is the mitochondrial permeability transi-
tion (MPT), phenomenon that is activated by ionic deregulation and
high production of reactive oxygen species (ROS). In this work we
have evaluated the mechanism by which the MPT apoptotic pathway
is activated in hearts from obese rats (mOb).
The results show that mitochondria from mOb were 2.5 and 3
times more susceptible to MPT than mitochondria from Lean rats
(mLean) when the respiratory chain was supplemented with
Glutamate–Malate (GM) or Glutamate–Succinate (GS). However, this
effect was not observed in the presence of Succinate-rotenone, as
substrate. In all experimental conditions, cyclosporine A (CSA)
protected the mitochondria, therefore, suggesting that the main
mechanism involved in the MPT is the high ROS production. Since the
NADH dehydrogenase is one of the enzymes that generate ROS, and,
under conditions of GS, the succinate dehydrogenase generates even
more ROS3, we analyzed the oxidative stress, ﬁnding higher
production of H2O2 in mOb than in mLean, mainly when the substrate
was GS. On the other hand, when the MPT was induced with
carboxiatractyloside (CAT), an inhibitor of the adenine nucleotide
translocase (ANT), the susceptibility to MPT was higher in mOb than
mLean, using GM as substrate and in the presence of CAT 1.5 μM, and
even more susceptible in the presence of GS and CAT 0.4 μM. Probably
because ROS is higher in mOb, and they may induce conformational
changes in mitochondrial proteins, increasing the binding of CAT and
accelerating the MPT. Finally, mitochondrial integrity was evaluated
by measuring respiration, and the results show that the respiratory
control and oxygen consumption in state 3 was lower in mOb; the
effect was observed only in the presence of GM. These results suggest
that ATP synthesis might be impaired due to decreased membrane
potential in mOb and contributes to MPT sensitivity. Conclusion: The
mOb has a higher sensibility to MPT than mLean and the principal
mechanism involved is the ROS production.
References
[1] C. Christoffersen, Endocrinology 144 (8) (2003) 3483–3490.
[2] B. Niemann, Y. Chen, M. Teschner, L. Li, R.-E. Silber, S. Rohrbach,
J. Am. Coll. Cardiol. 57 (5) (2011) 577–585.
[3] S.J. Ralph, R. Moreno-Sánchez, J. Neuzil, S. Rodríguez-Enríquez,
Pharm. Res. 28 (11) (2011) 2695–2730.
doi:10.1016/j.bbabio.2012.06.328
15P17
Anti-mitochondrial therapy in human breast
multi-cellular spheroids
S. Rodriguez-Enriquez, J.C. Gallardo-Perez, E.A. Mandujano-Tinoco,
R. Moreno-Sanchez
Instituto Nacional de Cardiología, Departamento de Bioquimica, México,
Mexico
Instituto Nacional de Cancerología, Laboratorio de Medicina
Translacional, México, Mexico
E-mail: saren960104@hotmail.com
During growth of solid tumors, gradients of oxygen and nutrients
develop inducing speciﬁc metabolic changes in the proliferative and
quiescent cellular layers. An integral analysis of proteomics, met-
abolomics, kinetomics and ﬂuxomics revealed that both enrich-
proliferative (PRL) and ‐quiescent (QS) cellular layers of mature
AbstractsS122


Obesity generates metabolic alterations in the myocardium leading to changes in mitochondrial membrane permeability 

Ajuntament de Barcelona

Repositori Obert de Coneixement de l'Ajuntament de Barcelona

Gaceta municipal de Barcelona. Año 048, nº 13 (27 mar. 1961)

Gaceta municipal de Barcelona. Año 048, nº 27 (03 jul. 1961)

Gaceta municipal de Barcelona. Año 048, nº 11 (13 mar. 1961)

Gaceta municipal de Barcelona. Año 048, nº 15 (10 abr. 1961)

Gaceta municipal de Barcelona. Año 048, nº 37 (11 sep. 1961)

Adriana Riojas

Flor E. Morales-Marroquín

Gerardo García-Rivas

⁎Noemí García

Crossref

Biochimica et Biophysica Acta (BBA) - Bioenergetics

Obesity generates metabolic alterations in the myocardium leading to changes in mitochondrial membrane permeability

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Obesity generates metabolic alterations in the myocardium leading to changes in mitochondrial membrane permeability

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