# name
White adipose tissue characterization and lipid profiling in obesity

# metadata.dc.contributor.other[].value
Universitat de Barcelona. Departament de Ciències Fisiològiques

# metadata.dc.description.abstract[].value
[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.

# metadata.dc.source[].value
Tesis Doctorals - Departament - Ciències Fisiològiques

# metadata.dc.title[].value
White adipose tissue characterization and lipid profiling in obesity