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Title: White adipose tissue characterization and lipid profiling in obesity
Author: Dahdah, Norma
Director/Tutor: García-Roves, Pablo M. (Pablo Miguel)
Malagón Poyato, María del Mar
Keywords: Teixit adipós
Trastorns del metabolisme
Trastorns del metabolisme dels lípids
Adipose tissues
Disorders of metabolism
Lipid metabolism disorders
Issue Date: 27-Jul-2022
Publisher: Universitat de Barcelona
Abstract: [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.
Appears in Collections:Tesis Doctorals - Departament - Ciències Fisiològiques

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