Obesity alters adipose tissue metabolic and endocrine function and leads to an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. To further characterize the changes that occur in adipose tissue with increasing adiposity, we profiled transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay) and obese (Lepob). We found that the expression of 1,304 transcripts correlated significantly with body mass. Of the 100 most significantly correlated genes, 30% encoded proteins that are characteristic of macrophages and are positively correlated with body mass. Immunohistochemical analysis of perigonadal, perirenal, mesenteric, and subcutaneous adipose tissue revealed that the percentage of cells expressing the macrophage marker F4/80 (F4/80+) was significantly and positively correlated with both adipocyte size and body mass. Similar relationships were found in human subcutaneous adipose tissue stained for the macrophage antigen CD68. Bone marrow transplant studies and quantitation of macrophage number in adipose tissue from macrophage-deficient (Csf1op/op) mice suggest that these F4/80+ cells are CSF-1 dependent, bone marrow-derived adipose tissue macrophages. Expression analysis of macrophage and nonmacrophage cell populations isolated from adipose tissue demonstrates that adipose tissue macrophages are responsible for almost all adipose tissue TNF-alpha expression and significant amounts of iNOS and IL-6 expression. Adipose tissue macrophage numbers increase in obesity and participate in inflammatory pathways that are activated in adipose tissues of obese individuals.

/pdf/obesity-is-associated-with-macrophage-accumulation-in-130af7ivca.pdf

Obesity is associated with macrophage accumulation in adipose tissue

http://aiocm.org/member/Immunity,%20Inflammation,%20and%20Cancer.pdf

Immunity, Inflammation, and Cancer

Metabolic and immune systems are among the most fundamental requirements for survival. Many metabolic and immune response pathways or nutrient- and pathogen-sensing systems have been evolutionarily conserved throughout species. As a result, immune response and metabolic regulation are highly integrated and the proper function of each is dependent on the other. This interface can be viewed as a central homeostatic mechanism, dysfunction of which can lead to a cluster of chronic metabolic disorders, particularly obesity, type 2 diabetes and cardiovascular disease. Collectively, these diseases constitute the greatest current threat to global human health and welfare.

/pdf/inflammation-and-metabolic-disorders-1u8s009p99.pdf

Inflammation and metabolic disorders

Insulin resistance arises from the inability of insulin to act normally in regulating nutrient metabolism in peripheral tissues Increasing evidence from human population studies and animal research has established correlative as well as causative links between chronic inflammation and insulin resistance However, the underlying molecular pathways are largely unknown In this report, we show that many inflammation and macrophage-specific genes are dramatically upregulated in white adipose tissue (WAT) in mouse models of genetic and high-fat diet-induced obesity (DIO) The upregulation is progressively increased in WAT of mice with DIO and precedes a dramatic increase in circulating-insulin level Upon treatment with rosiglitazone, an insulin-sensitizing drug, these macrophage-originated genes are downregulated Histologically, there is evidence of significant infiltration of macrophages, but not neutrophils and lymphocytes, into WAT of obese mice, with signs of adipocyte lipolysis and formation of multinucleate giant cells These data suggest that macrophages in WAT play an active role in morbid obesity and that macrophage-related inflammatory activities may contribute to the pathogenesis of obesity-induced insulin resistance We propose that obesity-related insulin resistance is, at least in part, a chronic inflammatory disease initiated in adipose tissue

/pdf/chronic-inflammation-in-fat-plays-a-crucial-role-in-the-1sc0uiuvmi.pdf

Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.

The metabolic syndrome

/pdf/martin-bell-fenotipi-gosteren-hastalarda-frajil-x-bulgulari-3wwdmjs0y1.pdf

Martin - bell fenoti̇pi̇ gösteren hastalarda fraji̇l x bulgulari

The present invention provides a method to identify and use compounds for the inhibition of abnormal or dysregulated hepatic glucose production that results in elevated blood glucose levels and associated metabolic disorders. The invention is based on the surprising discovery that the glucagon forms an obligate binding complex with aP2, which is necessary for activation of the glucagon G-coupled protein receptor.

Compounds useful to treat metabolic disorders

/pdf/author-correction-a-central-role-for-jnk-in-obesity-and-1jgo2ysb.pdf

Gurol Tuncman

Papers

Martin - bell fenoti̇pi̇ gösteren hastalarda fraji̇l x bulgulari

Compounds useful to treat metabolic disorders

Author Correction: A central role for JNK in obesity and insulin resistance