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White adipose tissue characterization and lipid profiling in obesity
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[eng] Obesity has become exceedingly pervasive, a resultant of amplified food availability
and reshaped human behavior stimulated by urbanization. It poses as a major
challenge for human metabolic physiology testing the limitations of metabolic
plasticity; an adaptive capacity against internal or environmental stressors. A stressor
persisting and turning into a chronic situation, diminishes the ability to adapt, thus
debilitating metabolic plasticity. In the face of the various strategies for combatting
obesity, it has become increasingly crucial to further advance the understanding of
obesity-associated metabolic adaptations at a systemic and a tissue-specific level.
Committed towards this purpose, the LiMa (Lifestyle Matters) project aimed at an
integrative multidisciplinary approach addressing phenotypical and functional
transitions induced by obesity and weight loss. A combined nutritional and exercise
intervention was implemented on a mouse model of diet-induced obesity in order to
evaluate metabolic plasticity and interpret the crosstalk among tissues and its
manifestation systemically. An assessment of several parameters, systemically and in
major tissues dictating metabolic responses, revealed an impressive capacity to
overcome the impairment induced by obesity. However, a lack of plasticity emphasized
by a deteriorating mitochondrial function in epididymal white adipose tissue (eWAT)
was evident in our study.
The aim of this doctoral thesis is to gain further insight on metabolic plasticity of
formerly obese mice by adding on to the description of the phenotypes of the
experimental groups and by focusing on different depots of white adipose tissue and
their stromal vascular fraction. A lipidomic study identified lipid profiles as tissue specific, and reported lipidomes of liver and skeletal muscle reflective of energy
balance contrary to eWAT lipidome, which was reflective of the content of the
administered diet. With the attention shifted towards adipose tissue, eWAT seemed to
be more susceptible than the other adipose tissue depot investigated – subcutaneous
white adipose tissue (sWAT) – to damage initiated by high-fat feeding. This
vulnerability was highlighted by an intense inflammatory profile, as indicated by the
M1 proinflammatory phenotype of infiltrating macrophages in eWAT and the presence
of crown-like structures surrounding adipocytes, together with worsening of
mitochondrial function of adipose-derived stem cells in eWAT. Moreover, other
macrophage subtypes seem to participate in eWAT expansion and remodeling,
including M2a macrophages induced by HFD, which are involved in endocytic
processes, as well as M2b macrophages, controlling the intensity of inflammatory
reactions, and M2c macrophages, involved in the phagocytosis of apoptotic adipocytes.
eWAT remodeling also involved significant changes in the composition and appearance
of the extracellular matrix, with HFD increasing the expression of both collagens and
proteoglycans involved in fibrosis, such as COL1, COL3 or COL6, and lumican and
versican, respectively. Notably, intervention studies aimed at reducing body weight
(exercise and decreased feeding) reverted, though only partially, the matrisome of
eWAT while the macrophage population recovered the original, lean phenotype upon
weight loss.
Hence, data from previous LiMa studies combined with data from this doctoral thesis
illustrate visceral white adipose tissue as the most affected tissue in the progression of
obesity. In addition, the deterioration in its mitochondrial function despite
improvements in tissue morphology hints at mitochondrial health as a key
determinator of the state of metabolic plasticity.
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DAHDAH, Norma. White adipose tissue characterization and lipid profiling in obesity. [consulta: 26 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/201008]