Extracellular Matrix Remodeling of Adipose Tissue in Obesity and Metabolic Diseases

The extracellular matrix (ECM) is a network of different proteins and proteoglycans that controls differentiation, migration, repair, survival, and development, and it seems that its remodeling is required for healthy adipose tissue expansion. Obesity drives an excessive lipid accumulation in adipocytes, which provokes immune cells infiltration, fibrosis (an excess of deposition of ECM components such as collagens, elastin, and fibronectin) and inflammation, considered a consequence of local hypoxia, and ultimately insulin resistance. To understand the mechanism of this process is a challenge to treat the metabolic diseases. This review is focused at identifying the putative role of ECM in adipose tissue, describing its structure and components, its main tissue receptors, and how it is affected in obesity, and subsequently the importance of an appropriate ECM remodeling in adipose tissue expansion to prevent metabolic diseases.

Association of Immune and Metabolic ReceptorsC5aRandC5L2with Adiposity in Women

Adipose tissue receptorsC5aRandC5L2and their heterodimerization/functionality and interaction with ligandsC5aand acylation stimulating protein (ASP) have been evaluated in cell and rodent studies. Their contribution to obesity factors in humans remains unclear. We hypothesized thatC5areceptors, classically required for host defense, are also associated with adiposity. Anthropometry and fasting blood parameters were measured in 136 women divided by body mass index (BMI): normal/overweight (≤30 kg/m2;n= 34), obese I (≤45 kg/m2;n= 33), obese II (≤51 kg/m2;n= 33), and obese III (≤80 kg/m2;n= 36). Subcutaneous and omental adipose tissueC5aRandC5L2expression were analysed.C5L2expression was comparable between subcutaneous and omental across all BMI groups. Plasma ASP and ASP/omentalC5L2expression increased with BMI (P< 0.001 andP< 0.01, resp.). While plasmaC5awas unchanged,C5aRexpression decreased with increasing BMI in subcutaneous and omental tissues (P< 0.01 andP< 0.05, resp.), with subcutaneous omental depots. OmentalC5L2/C5aRratio increased with BMI (P< 0.01) with correlations betweenC5L2/C5aRand waist circumference, HDL-C, and adiponectin. Tissue and BMI differences in receptors and ligands, particularly in omental, suggest relationship to metabolic disturbances and highlight adipose-immune interactions.

Evidence for cross-talk between stanniocalcins

There are 2 forms of stanniocalcin (STC) produced by the STC-1 gene; a 50 kDa polypeptide known as STC50 and a recently discovered group of higher molecular weight variants that are collectively referred to as big STC. Both have different tissue patterns of expression and different intracellular targeting pathways. STC50 functions locally in tissues such as muscle, liver, and kidney and is targeted to mitochondria. Big STC, on the other hand, is made by the ovaries. It signals both locally on nearby corpus luteal cells and systemically. Interestingly, however, receptor binding assays employing STC50 as the tracer have shown that the smaller ligand can bind equally to tissue receptors targeted by either form of the hormone. This suggests there may be cross-talk between ligands. The present study provides credence to this notion by demonstrating how the 2 hormones can compete for tissue receptors normally targeted by 1 form of the hormone (big STC). The results also reveal how STC50 can completely block the inhibitory effects of big STC on luteal cell progesterone release when added simultaneously. The findings therefore add credence to the possibility that there may be circumstances during which the 2 ligands functionally antagonize each other's actions.Key words: stanniocalcin (STC), STC50, big STC, receptor, antagonism, progesterone release.

Regulation of nutrient partitioning growth and lactation

This paper will emphasize the impact of growth and lactation on partitioning nutrients, the role of biological signals and whether such signals can be influenced or modified. Factors considered are the mechanisms of controlling cell cycling, growth and differentiation; interaction or cross-talking between tissues (autocrinepeptides, tissue receptors, secondary messengers); effect of extrinsic and intrinsic signals on cellular growth (growth hormones, oncogenes); and manipulation of nutrient partitioning (mutated receptors, gene expression, targeting metabolic genes).

Intact transferrin receptors in human plasma and their relation to erythropoiesis

Intact transferrin receptor molecules complexed with transferrin were found in human plasma. The concentration of receptors was determined by an enzyme-linked immunosorbent assay that uses polyclonal antibodies. The mean concentration of 8,279 micrograms/L in 56 normal adults appears to be unrelated to age or sex. Additional receptor measurements were performed on plasmas from 260 subjects with erythropoietic disorders. Decreased concentration of plasma receptors was found in patients with erythroid hypoplasia and increased numbers in those with erythroid hyperplasia. Ferrokinetic measurements of erythropoiesis were compared with numbers of receptors in 148 subjects, and a close correlation was found (r = .86). Both sets of values, measured in different conditions and expressed in relation to normal, were consistent with expected values. Receptor values were unproportionally increased only in conditions of iron deficiency. It is concluded that plasma receptors have a constant relationship to tissue receptors, and their number in most instances reflects the rate of erythropoiesis.

Intact transferrin receptors in human plasma and their relation to erythropoiesis

Intact transferrin receptor molecules complexed with transferrin were found in human plasma. The concentration of receptors was determined by an enzyme-linked immunosorbent assay that uses polyclonal antibodies. The mean concentration of 8,279 micrograms/L in 56 normal adults appears to be unrelated to age or sex. Additional receptor measurements were performed on plasmas from 260 subjects with erythropoietic disorders. Decreased concentration of plasma receptors was found in patients with erythroid hypoplasia and increased numbers in those with erythroid hyperplasia. Ferrokinetic measurements of erythropoiesis were compared with numbers of receptors in 148 subjects, and a close correlation was found (r = .86). Both sets of values, measured in different conditions and expressed in relation to normal, were consistent with expected values. Receptor values were unproportionally increased only in conditions of iron deficiency. It is concluded that plasma receptors have a constant relationship to tissue receptors, and their number in most instances reflects the rate of erythropoiesis.