Metabolomic Profiling Reveals Mitochondrial-Derived Lipid Biomarkers That Drive Obesity-Associated Inflammation

Obesity has reached epidemic proportions worldwide. Several animal models of obesity exist, but studies are lacking that compare traditional lard-based high fat diets (HFD) to “Cafeteria diets" (CAF) consisting of nutrient poor human junk food. Our previous work demonstrated the rapid and severe obesogenic and inflammatory consequences of CAF compared to HFD including rapid weight gain, markers of Metabolic Syndrome, multi-tissue lipid accumulation, and dramatic inflammation. To identify potential mediators of CAF-induced obesity and Metabolic Syndrome, we used metabolomic analysis to profile serum, muscle, and white adipose from rats fed CAF, HFD, or standard control diets. Principle component analysis identified elevations in clusters of fatty acids and acylcarnitines. These increases in metabolites were associated with systemic mitochondrial dysfunction that paralleled weight gain, physiologic measures of Metabolic Syndrome, and tissue inflammation in CAF-fed rats. Spearman pairwise correlations between metabolites, physiologic, and histologic findings revealed strong correlations between elevated markers of inflammation in CAF-fed animals, measured as crown like structures in adipose, and specifically the pro-inflammatory saturated fatty acids and oxidation intermediates laurate and lauroyl carnitine. Treatment of bone marrow-derived macrophages with lauroyl carnitine polarized macrophages towards the M1 pro-inflammatory phenotype through downregulation of AMPK and secretion of pro-inflammatory cytokines. Results presented herein demonstrate that compared to a traditional HFD model, the CAF diet provides a robust model for diet-induced human obesity, which models Metabolic Syndrome-related mitochondrial dysfunction in serum, muscle, and adipose, along with pro-inflammatory metabolite alterations. These data also suggest that modifying the availability or metabolism of saturated fatty acids may limit the inflammation associated with obesity leading to Metabolic Syndrome

Consequences of Realism for Sociological Theory-Building

It is argued that the Achilles heel of contemporary sociology – and great parts of social science – is a) weak theory development, and b) absence of a meta-theory providing a common platform and a shared goal for its practitioners, fostering cumulativity. A meta-theory called causal realism (a variant of critical realism) is suggested for these purposes. The main tenets and key concepts of realism, such as causality and explanation, mechanism, stratified reality, are presented. Thereafter, via an analogy to the physical sciences, it is argued that a natural implication of realism and the search for causal mechanisms is a division of society into levels. The micro-macro issue is approached by a level-ontology for the development of sociological theory. Five levels are suggested, discussed and briefly exemplified. In the concluding remarks, some further positive implications of realism to sociology are touched upon

Theorizing the Professions. Outline to an explanatory model.

In a previous article (published in Professional Identities in Transition, 1999) I invented two macro-sociological concepts for capturing the historical development of professions, called professional types and professional waves. Even though Sweden was used as the sole empirical base for the two concepts, it was claimed that they would be applicable to other professions, especially Continental ones. In this paper I seek to demonstrate this, not by applying the concepts to other empirical examples but by discussing them from a meta-theoretical point of view. In particular, I seek to explore a) their philosophical foundations, and b) their capability of being extended to explanatory models of the historical development and contemporary standing of modern professions, i.e., the professions are approached from diachronic as well as synchronic macro-sociological perspectives