Summary: | Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of liver disease in the Western
world, affecting up to 20-30% of the general adult population. It is a growing public health problem, because of
the increasing prevalence of the pathologies that contribute to its development such as obesity and inflammation
status. The diagnostic method of choice for NAFLD is liver biopsy, but since it is a long-standing disease, it is
difficult to follow large population groups through serial biopsies. Therefore, it is necessary to identify noninvasive
liver damage tools that facilitate the diagnosis and prognosis of the disease and allow for the
establishment of a follow-up protocol that prevents progression to severe stages of NAFLD. Moreover, the main
therapeutic basis is the modification of lifestyle through diet and exercise In this context, this research work
aimed: 1) to assess the possible association between a validated Dietary Inflammatory Index (DII) and specific
dietary components with suitable non-invasive markers of liver status in overweight/obese subjects with
cardiovascular risk; 2) to evaluate the influence of two energy-restricted diets on non-invasive markers and
scores of liver damage in overweight/obese individuals with features of metabolic syndrome after six months of
follow-up and to assess the role of fiber content in metabolic outcomes; 3) to assess the influence of weight loss
on lysophospholipid metabolism and liver status in overweight/obese subjects as well as to provide new
evidence regarding the interaction of lysophospholipids metabolism as a key factor in the onset and management
of obesity-related diseases such as liver damage; 4) to analyze the response of FGF-21 after a weight loss
intervention and the relationships with other putative inflammatory liver biomarkers; 5) to evaluate the fatty liver
status by several validated approaches and to compare imaging techniques, lipidomic and routine blood markers
with magnetic resonance imaging (MRI) in adults subjects with NAFLD. In relation with the first objective, the
results of this chapter evidended that the consumption of an anti-inflammatory dietary pattern might contribute
to the reduction of obesity and related comorbidities, especially NAFLD through precision nutrition guidelines.
Concerning the second objective, we concluded that the design of dietary patterns based on the consumption of
insoluble fiber and fiber from fruits in the context of energy restriction is a good choice the management of
obese patients suffering from NAFLD. The third chapter suggested a generalized decrease in circulating
lysophospholipids (LP), particularly lysophosphatidylcholine, after a weight loss intervention in a population
with metabolic syndrome features. Changes in fatty liver index, waist circumference and BAAT score revealed
positive association with lysophosphatidylcholine score. The involvement of particular LP in liver metabolism
and obesity merits further attention. The fourth chapter revealed that FGF-21 changes exhibit a great association
with non-alcoholic fatty liver inflammation, M30 fragment and PAI-I, independently of weight loss. These
findings suggest that FGF-21 is involved in the obesity-inflammation-liver process. Finally, in relation to the
fifth objective we concluded that ultrasonography, a metabolomic test and a panel combination including routine
blood markers linked to insulin resistance showed the highest associations with MRI, which is considered the
gold standard for non-invasive liver fat content assessment, suggesting these tools could contribute to the
diagnosis and prognosis of NAFLD.
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