The obesity epidemic has forced us to evaluate the role of inflammation in the health complications of obesity. This has led to a convergence of the fields of immunology and nutrient physiology and the understanding that they are inextricably linked. The reframing of obesity as an inflammatory condition has had a wide impact on our conceptualization of obesity-associated diseases. In this Review, we highlight the cellular and molecular mechanisms at play in the generation of obesity-induced inflammation. We also emphasize how defining the immune regulation in metabolic tissues has broadened the understanding of the diversity of inflammatory responses.

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Inflammatory links between obesity and metabolic disease.

Mechanisms for insulin resistance: common threads and missing links.

Accumulating evidence indicates that obesity is closely associated with an increased risk of metabolic diseases such as insulin resistance, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease. Obesity results from an imbalance between food intake and energy expenditure, which leads to an excessive accumulation of adipose tissue. Adipose tissue is now recognized not only as a main site of storage of excess energy derived from food intake but also as an endocrine organ. The expansion of adipose tissue produces a number of bioactive substances, known as adipocytokines or adipokines, which trigger chronic low-grade inflammation and interact with a range of processes in many different organs. Although the precise mechanisms are still unclear, dysregulated production or secretion of these adipokines caused by excess adipose tissue and adipose tissue dysfunction can contribute to the development of obesity-related metabolic diseases. In this review, we focus on the role of several adipokines associated with obesity and the potential impact on obesity-related metabolic diseases. Multiple lines evidence provides valuable insights into the roles of adipokines in the development of obesity and its metabolic complications. Further research is still required to fully understand the mechanisms underlying the metabolic actions of a few newly identified adipokines.

Obesity and Its Metabolic Complications: The Role of Adipokines and the Relationship between Obesity, Inflammation, Insulin Resistance, Dyslipidemia and Nonalcoholic Fatty Liver Disease

It is now recognized that obesity is driving the type 2 diabetes epidemic in Western countries Obesity-associated chronic tissue inflammation is a key contributing factor to type 2 diabetes and cardiovascular disease, and a number of studies have clearly demonstrated that the immune system and metabolism are highly integrated Recent advances in deciphering the various cellular and signaling networks that participate in linking the immune and metabolic systems together have contributed to understanding of the pathogenesis of metabolic diseases and may also inform new therapeutic strategies based on immunomodulation Here we discuss how these various networks underlie the etiology of the inflammatory component of insulin resistance, with a particular focus on the central roles of macrophages in adipose tissue and liver

The cellular and signaling networks linking the immune system and metabolism in disease

The 1921 discovery of insulin was a Big Bang from which a vast and expanding universe of research into insulin action and resistance has issued. In the intervening century, some discoveries have ma...

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Mechanisms of Insulin Action and Insulin Resistance

Obesity is associated with an enhanced inflammatory response that exacerbates insulin resistance and contributes to diabetes, atherosclerosis, and cardiovascular disease. One mechanism accounting for the increased inflammation associated with obesity is activation of the innate immune signaling pathway triggered by TLR4 recognition of saturated fatty acids, an event that is essential for lipid-induced insulin resistance. Using in vitro and in vivo systems to model lipid induction of TLR4-dependent inflammatory events in rodents, we show here that TLR4 is an upstream signaling component required for saturated fatty acid–induced ceramide biosynthesis. This increase in ceramide production was associated with the upregulation of genes driving ceramide biosynthesis, an event dependent of the activity of the proinflammatory kinase IKKβ. Importantly, increased ceramide production was not required for TLR4-dependent induction of inflammatory cytokines, but it was essential for TLR4-dependent insulin resistance. These findings suggest that sphingolipids such as ceramide might be key components of the signaling networks that link lipid-induced inflammatory pathways to the antagonism of insulin action that contributes to diabetes.

/pdf/lipid-induced-insulin-resistance-mediated-by-the-5fwii9vai9.pdf

Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice.

Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation, and Metabolism.

ABSTRACT Objective To evaluate the influencing factors and cognitive functional changes in Rasmussen encephalitis (RE) patients who received a hemispherectomy. Methods Forty RE patients underwent a hemispherectomy with at least a 2 years follow- up were included in this study . Postoperative seizure outcomes were evaluated according to the Engle classification scale. Univariate analysis and a multivariate logistic regression model in a backward fashion were used to identify the potential predictors of cognitive function. Results All 40 patients had an Engle classification outcome at a 2 years follow-up. Univariate and multivariate analyses revealed that seizure duration (OR 10.06, 95% CI 1.54–3.85, p = 0.038), age at surgery (OR 3.06, 95% CI 1.21–3.56, p = 0.043), and MRI score (OR 0.09, 95% CI 0.01–0.67 p = 0.024) are associated with postoperative cognitive outcomes respectively. Moreover, VIQ and PIQ were negatively correlated linearly with duration of seizures and MRI score. Patients with a good VIQ and PIQ before the operation were more likely to have a better VIQ and PIQ postoperatively (p < 0.001 and p < 0.001, respectively). And, operation side is an important factor affecting cognitive function; therefore, a left hemispherectomy has a greater impact on the patient’s IQ and language. Conclusions RE patients’ cognitive dysfunctions are improved after a hemispherectomy. Right-side operation can achieve better postoperative cognitive outcomes especially in VIQ and language. A shorter duration of seizures, early age at surgery, and less severe brain atrophy suggest better cognitive outcomes after a hemispherectomy.

https://figshare.com/articles/journal_contribution/The_influencing_factors_and_changes_of_cognitive_function_within_40_Rasmussen_encephalitis_patients_that_received_a_hemispherectomy/19187781

Guan Yuguang

Papers

Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice.

Adipocyte Ceramides Regulate Subcutaneous Adipose Browning, Inflammation, and Metabolism.

The influencing factors and changes of cognitive function within 40 Rasmussen encephalitis patients that received a hemispherectomy