Adipose tissue, development

Barak, Y., Hao, D., Weimin, H. et al. (2002) Effects of peroxisome proliferator-activated receptor 8 on placentation, adiposity, and colorectal cancer. Proceedings of the National Academy of Sciences of the United States of America, 99, 303—308. Barak, Y., Nelson, M.C., Ong, E.S. et al. (1999) PPARy is required for placental, cardiac, and adipose tissue development. Molecular Cell, 4, 585—595. 

Nevertheless, interest in the lipid phosphate phosphatases continues to flourish, not least because of their therapeutic potential. For example, lipid phosphate phosphatase activity is reduced in ra -transformed cells (Martin et al., 1993), regulates adipose tissue development (Simon et al., 2002) and reduces the growth and survival of ovarian cancer cells, which may provide a novel strategy for the treatment of this and other cancers (Tanyi et al., 2003). A parallel may be drawn here with PAF acetylhydrolase, which inactivates PAF. Indeed, the recombinant form of this enzyme has been used to reduce oedema and vascular leakage in addition to inflammation in enterocolitis, pancreatitis and diabetes (Prescott et al., 2000). 

My interest in avian adipose tissue developed in a somewhat devious way, as a consequence of observations about the effect of glucagon on the serum lipids of hyperlipemic human subjects. We found that daily repeated glucagon injection caused a marked decrease of the various lipid fractions (cholesterol, phospholipids, total fatty acids), followed by an elevation when the administration of the hormone was discontinued. This and other observations - suggested a role of glucagon in the regulation of lipid metabolism, and I decided to look into the question. 

Smith, S.B., H. Kawachi, C.B. Choi, C.W. Choi, G. Wu and J.E. Sawyer, 2009. Cellular regulation of bovine intramuscular adipose tissue development and composition. J Anim Sci. 87(14 Suppl), E72-82. 

Symonds, M.E., S. Pearce, J. Bispham, D.S. Gardner, and T. Stephenson, 2004. Timing of nutrient restriction and programming of fetal adipose tissue development. Proc. Nutr. Soc. 63, 397-403. 

It is fortunate that the development of adipose tissue lipids in man can be studied with relatively simple biopsy techniques. Detailed temporal studies of human brain lipids are more problematical and highlight the need for a good animal model. The pig, which is inadequate as a model for the temporal aspects of adipose tissue development, is useful as a model for... 

The wide range of inflammation-related factors that adipocytes secrete is linked to the inflammatory response that the tissue exhibits in obesity [1]. Obesity in general, like an increasing number of other diseases, is characterised by a state of mild chronic inflammation, and adipose tissue plays a central role in this. The production of most inflammation-related adipokines increases markedly in obesity and there is an elevated circulating level of a number of these factors as well as of other inflammatory markers such as C-reactive protein (CRP). The increased production of inflammatory adipokines (and decreased production of adiponectin with its anti-inflammatory action) in the obese is considered to play a critical role in the development of the obesity-associated pathologies, particularly type 2 diabetes and the metabolic syndrome [1]. 

Little attempt has been made to develop drugs targeted specifically to white adipose tissue and the production of adipokines. It is likely, however, that there will be an increasing emphasis on this approach to the pharmacological treatment of obesity-related diseases, given the current views on the centrality of the adipokines to these disorders. It is, of course, the diseases that obesity leads to, rather than obesity itself, that constitute the main medical challenge. 

There has been considerable focus on the development of drugs that lead to a reduction in the total amount of adipose tissue. These include agents targeted at limiting fat absorption, the inhibition of appetite, and the stimulation of energy expenditure (thermogenesis)-or a combination thereof. The best example of drugs,... 

The first hormonal signal found to comply with the characteristics of both a satiety and an adiposity signal was insulin [1]. Insulin levels reflect substrate (carbohydrate) intake and stores, as they rise with blood glucose levels and fall with starvation. In addition, they may reflect the size of adipose stores, because a fatter person secretes more insulin than a lean individual in response to a given increase of blood glucose. This increased insulin secretion in obesity can be explained by the reduced insulin sensitivity of liver, muscle, and adipose tissue. Insulin is known to enter the brain, and direct administration of insulin to the brain reduces food intake. The adipostatic role of insulin is supported by the observation that mutant mice lacking the neuronal insulin receptor (NDRKO mice) develop obesity. 

Leptin is a cytokine produced and secreted by adipose tissue in proportion to the body fat content [3]. Mice and humans lacking leptin or its receptor develop a severe hyperphagia and a dramatic degree of obesity which is considerably more pronounced than that of the NDRKO mouse. Thus, leptin is the key adiposity signal in rodents and humans. Leptin secretion appears to reflect the metabolic status of the adipocyte rather than the sheer size of triglyceride deposits, and leptin levels may transiently be dissociated from total body fat. Nonetheless, over the course of a day with unrestricted food supply, plasma leptin levels reliably reflect the amount of total body fat. Local administration of leptin into the brain results in reduced food intake. The vast majority of patients with obesity have elevated serum levels of leptin. Thus, it is believed that the polygenic obesity is due to leptin resistance rather than to inadequate leptin secretion, or to a reduced blood/brain transport of the cytokine. 

The overall results and individual PBPK models for trichloroethylene are discussed in this section in terms of their use in risk assessment, tissue dosimetry, and dose, route, and species extrapolations. Several PBPK models have been developed for inhaled trichloroethylene. In an early model by Fernandez et al. (1977), the human body was divided into three major compartments or tissue groups the vessel-rich group (VRG), muscle group (MG), and adipose tissue (fat) group (FG). The distribution of trichloroethylene in these... 

Matsumoto et al. developed an immunoassay for the determination of clenbuterol in bovine and equine tissues and in bovine milk. The LOD of clenbuterol in milk, muscle, liver, kidney, small intestine, and adipose tissues was 0.1 qgkg Bovine tissue samples fortified wifh 1 qg kg of clenbuterol had recoveries that varied from 75 to 96%, but recoveries from milk samples were 99%. The authors utilized this method to estimate the clenbuterol withdrawal periods for cattle and horses. Cattle were treated with a bolus dose of either 0.3 or 0.6 qg kg body weight, by intravenous injection, and three animals were slaughtered at days 1, 6, and 9. Tissue clenbuterol levels were detectable only on day 1. Clenbuterol in milk was not detectable after a 2.5-day withdrawal period. Liver contained the highest clenbuterol concentration of the tissues measured, but this group did not measure eye tissues. 

A wet-ashing procedure for analysis of fatty animal tissue was modified by using Teflon-lined bombs rated for use at 340 bar instead of open crucibles. Bombs cooled to well below 0°C were charged with fuming nitric and fuming sulfuric acids (1 ml of each) and adipose tissue (0.5 g), removed from the cooling bath and sealed. After 10 min delay, the bombs exploded, probably owing to development of... 

A method with LOQ at ppt levels was developed based on LLE followed by GC-AFID for the determination of trace concentrations of nitrobenzene, l-chloro-2-nitrobenzene and synthetic fragrances such as musk xylene (223) and musk ketone (224). The method was applied to study the distribution of these compounds in environmental samples of North Sea waters460. GC with atomic emission detection (AED) has been successfully applied to the determination of nitro musks in human adipose tissues, at ppb concentration levels. A clean-up procedure for nonpolar substances and element-specific detection with AED enabled for the first time target screening analysis for lipophilic nitro aromatic compounds. The lack of sensitivity of AED was compensated by higher concentrations of the extracts... 

Khat produces sympathomimetic effects, increasing heart rate and blood pressure. When khat is chewed, the increases are gradual, maximizing at about 2 hours and lasting for 4 hours. However, tolerance develops to blood pressure and heart rate effects in habitual users. Mydriasis and increases in respiration also occur. Cathinone induces thermogenesis in brown adipose tissue, which is mediated by jS-adrenergic receptors (Tariq et al. 1989). 

In patients with type 1 insulin-dependent diabetes mellitus not adequately treated with insulin, fatty add release from adipose tissue and ketone synthesis in the liver exceed the ability of other tissues to metabolize them, and a profound, life-threatening ketoaddosis may ocxnir. An infection or trauma (causing an increase in cortisol or epinephrine) may predpitate an episode of ketoaddosis. Patients with type 2 non-insulin-dependent diabetes meUitus (NIDDM) are much less likely to show ketoaddosis. The basis for this observation is not completely understood, although type 2 disease has a much slower, insidious onset, and insulin resistance in the periphery is usually not complete. Type 2 diabetics can develop ketoacidosis after an infection or trauma. In certain populations with NIDDM, ketoaddosis is much more common than previously appredated. 

Extremely sensitive analytical methods have been developed for the detection of heptachlor and heptachlor epoxide in various environmental and biological samples (detection limits as low as 10 ng/L). Although most methods were developed for detecting heptachlor and heptachlor epoxide in environmental media, the technology is readily adaptable to biological materials including breast milk, adipose tissue, and serum. These methods can be used to determine whether exposure has occurred. The presence of heptachlor may reflect an exposure to heptachlor or chlordane because it is a metabolite of chlordane. The presence of heptachlor epoxide may reflect an exposure to heptachlor or to chlordane since it is a metabolite of both these pesticides. However, in the absence of stable chlordane residues (e.g., nonachlor and oxychlordane), the heptachlor epoxide would most likely have been derived from heptachlor. 

I have already mentioned leptin. There are several others, notably including adiponectin, a protein present in high concentrations in blood. Adiponectin is an antihyperglycemic agent, acting to increase insulin sensitivity. There is a close relationship between obesity, insulin action, and development of type 2 diabetes. Withont listing additional peptides secreted by adipose tissue, it is important to understand that fat is an important player in human physiology. 

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