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Unsaturated Fatty Acids

Animal fats contain a high proportion of glyc-erides of saturated fatty acids and tend to be solids, whilst those from plants and fish contain predominantly unsaturated fatty acid esters and tend to be liquids. Some of the common naturally occurring unsaturated fatty acids are also included in Table 3.1. A convenient shorthand representation for fatty acids indicating chain length with number, position and stereochemistry of double bonds is also presented in Table 3.1. A less systematic numbering starting from the methyl (the m end) may also be encountered. Major groups of fatty acids are designated m-3 (omega-3), m-6 (omega-6), m-9 (omega-9), etc (or sometimes n-3, n-6, n-9), if there is a double bond that number of carbons from the methyl terminus. This has some value in relating structures when an unsaturated fatty acid is biosynthetically elongated from the carboxyl end as during prostaglandin biosynthesis (see page 45). Double bonds at position 9 are common, but unsaturation can...

Saturated and trans fatty acids in the diet

Saturated fatty acids (SAFAs) have no double bonds. They primarily come from animal products such as meat and dairy products, and from tropical oils such as palm oil, palm kernel oil, and coconut fat. In general, such fats are solid at room temperature. Stearic acid is a saturated fatty acid that may have different biological effects from other saturated fatty acids. Important food sources of stearic acid are beef, hydrogenated vegetable oils and chocolate. Monounsaturated fatty acids (MUFAs) have one double bond. Plant sources that are rich in MUFAs are liquid vegetable oils, such as rapeseed oil, olive oil, high-oleic sunflower oil, and nuts. Polyunsaturated fatty acids (PUFAs) have two or more double bonds. The large majority of PUFA in the diet (90 or more) is linoleic acid, an n-6 (or omega-6) fatty acid. Vegetable oils such as soybean, rapeseed and sunflower oils are important sources. PUFAs also occur as the n-3 (or omega-3) fatty acid alpha-linolenic acid in some vegetable...

Lipoprotein Metabolism

Chylomicrons are assembled in the enterocytes of the small intestine after ingestion of dietary fat (triglyceride) and cholesterol. In the lymph and the blood, chylomicrons acquire several apolipoproteins, including apo C-II, apo C-III, and apo E. In the capillary beds of adipose tissue and muscle, chylomicrons interact with the enzyme lipoprotein lipase (LPL), which is activated by apo C-II, and the chylomicron core triglyceride is hydrolyzed. The lipolytic products, free fatty acids, can be taken up by fat cells where they are converted back into triglyceride, or by muscle cells, where they can be used for energy. Apo C-III can inhibit lipolysis, and the balance of apo C-II and apo C-III determines, in part, the efficiency with which LPL hydrolyzes chylomicron triglyceride. The product of this lipolytic process is the chylomicron remnant, which has only about 25 of the original chylomicron triglyceride remaining. Importantly, the chylomicron remnants are relatively enriched in...

An Example of an Organ The Skin

The skin is nourished by blood vessels within the dermis. In addition to blood vessels, the dermis contains wandering white blood cells and other types of cells that protect against invading disease-causing organisms. It also contains nerve fibers and fat cells however, most of the fat cells are grouped together to form the hypodermis (a layer beneath the dermis). Although fat cells are

Lymphoid Cells and Organs Evolutionary Comparisons

Myeloid Stem Cell Development

In bone marrow, hematopoietic cells grow and mature on a meshwork of stromal cells, which are nonhematopoietic cells that support the growth and differentiation of hema-topoietic cells. Stromal cells include fat cells, endothelial cells, fibroblasts, and macrophages. Stromal cells influence the differentiation of hematopoietic stem cells by providing a hematopoietic-inducing microenvironment (HIM) consisting of a cellular matrix and factors that promote growth and differentiation. Many of these hematopoietic growth factors are soluble agents that arrive at their target cells by diffusion, others are membrane-bound molecules on the surface of stromal cells that require cell-to-cell contact between the responding cells and the stromal cells. During infection, hematopoiesis is stimulated by the production of hematopoietic growth factors by activated macrophages and T cells.

The Fightor Flight Response Is a Result of Widespread Sympathetic Activation

Sympathetic stimulation of the heart and blood vessels results in a rise in blood pressure because of increased cardiac output and increased total peripheral resistance. There is also a redistribution of the blood flow so that the muscles and heart receive more blood, while the splanchnic territory and the skin receive less. The need for an increased exchange of blood gases is met by acceleration of the respiratory rate and dilation of the bronchiolar tree. The volume of salivary secretion is reduced but the relative proportion of mucus increases, permitting lubrication of the mouth despite increased ventilation. The potential demand for an enhanced supply of metabolic substrates, like glucose and fatty acids, is met by the actions of the sympathetic nerves and circulating epinephrine on hepato-cytes and adipose cells. Glycogenolysis mobilizes stored liver glycogen, increasing plasma levels of glucose. Lipol-ysis in fat cells converts stored triglycerides to free fatty acids that...

Genetic influences on the metabolic syndrome

It has long been thought that obesity precedes the metabolic syndrome, but it is now known that this syndrome can be observed in lean subjects, even if its prevalence increases in a graded fashion as body weight increases (St-Onge et al., 2004). Recent findings about the endocrine (but also paracrine and autocrine) function of adipocytes have renewed interest in the topic. Indeed, it has been demonstrated that fat cells are able to secrete pro-inflammatory and insulin resistance-inducing cytokines (TNF-alpha, resistin), as well as molecules acting in concert to facilitate glucose uptake (adiponectin) or the central control of satiety (leptin) (Lafontan, 2005). Accordingly, candidate genes for predisposition to the metabolic syndrome are those involved in the fat cell metabolism, including secreted adipokines, or the insulin signalling pathway acting in liver, muscle or fat cells. Some of them have already been described above, those associated with dyslipidaemia (Laakso, 2004), such...

Clinical Focus Box 321

GH is also thought to function as one of the counter-regulatory hormones that limit the actions of insulin on muscle, adipose tissue, and the liver. For example, GH inhibits glucose use by muscle and adipose tissue and increases glucose production by the liver. These effects are opposite those of insulin. Also, GH makes muscle and fat cells resistant to the action of insulin itself. Thus, GH normally has a tonic inhibitory effect on the actions of insulin, much like the glucocorticoid hormones (see Chapter 34).

Mangs Spacelift Introduction

The name spacelift was chosen by the author and protected by patent (no. 30323891) as appropriately purified and centrifugated, recycled fat droplets are injected into the entire face, as in a honeycomb, using microinjections. The fat particles break down but, as a result of the contact with vessels (because they are not injected in large quantities in a bolus dose), they are able to form their own fibroblasts and the catabo-lized fat cells are augmented with fibroblasts and elastin fibers. Virtually no scars are formed and the face stabilizes as a result of the procedure. Naturally, injections can be made beneath other wrinkles in the forehead and nasolabial area using a conventional fat injection technique. Lipo-transfer is also recommended for lip augmentation.

The Hypothalamus Regulates Eating Behavior

Arcuate Nucleus Third Ventricle

A key player in the regulation of body weight is the hormone leptin, which is released by white fat cells (adipocytes). As fat stores increase, plasma leptin levels increase, conversely, as fat stores are depleted, leptin levels decrease. Cells in the arcuate nucleus of the hypothalamus appear to be the sensors for leptin levels. Physiological responses to low leptin levels (starvation) are initiated by the hypothalamus to increase food intake, decrease energy expenditure, decrease reproductive function, decrease body temperature, and increase parasympathetic activity. Physiological responses to high leptin levels (obesity) are initiated by the hypothalamus to decrease food intake, increase energy expenditure, and increase sympathetic activity. Hypothalamic pathways involving neuropeptide Y are important for the starvation response, while pathways involving the melanocyte-stimulating hormone are important for the obesity response.

Lipolysis and Reesterification

Adipose Tissue Interstitial Space

The temporal and spatial relationship between breakdown (lipolysis) and re-synthesis (re-esterification) of TAG (TAG-FA cycling) has to be tightly controlled to either provoke or avoid generation of heat and energy expenditure through the utilization of ATP during substrate cycling. A substrate cycle exists when opposing, non-equilibrium reactions catalyzed by different enzymes are operating simultaneously 23, 24 . At least one of the reactions must involve the hydrolysis of ATP. Thus, a substrate cycle both liberates heat and increases energy expenditure in the absence of net conversion of substrate into product. Some of the NEFA formed during lipolysis can be re-esterified to TAG 25, 26 , whereas little or no glycerol is re-utilized by fat cells 27 . This pathway of lipolysis and NEFA re-ester-ification forms an important cycle for energy turnover, allowing the fat cell to respond rapidly to changes in peripheral requirements for NEFA (Fig. 11.1). This is reflected in the FA...

Ftiii The hormones insulin and glucagon I 0 control fuel metabolism

' f During the absorptive period, blood glucose levels rise as carbohydrates are digested and absorbed. During this time, the P cells of the pancreas release a hormone called insulin (see Chapter 42). Insulin plays a major role in directing glucose to where it will be used or stored. Insulin enhances the uptake of glucose from the blood and its conversion to glycogen by liver and muscle cells. It stimulates fat cells to take up glucose from the blood and convert it to stored fat, and it stimulates cells in most tissues of the body to preferentially use glucose as their metabolic fuel.

Involvement of Lipotransin

Translocation of HSL to LD might be prevented in unstimulated cells by a cytosolic inhibitor protein which interacts with HSL or by a LD-associated protein which prevents HSL gaining access to the LD surface, as has been proposed for perilipin (see above). Alternatively, HSL might interact with a LD-associated docking protein upon activation, facilitating its translocation to the LD. Saltiel and coworkers have identified a novel binding-protein for HSL, called lipotransin, that fulfils several criteria for an HSL docking protein 266 . It can bind directly to HSL, as demonstrated in two-hybrid assays, and in in vitro pulldown experiments. The two proteins form a complex in coprecipitation experiments from cells transfected to overexpress the proteins, as well as in fat cells expressing endogenous levels. HSL and lipotransin are detected in overlapping but not identical adipocyte cellular fractions. However, in response to lipolytic agents, HSL translocates to a lipid membrane fraction...

Adipose Tissue Stores and Supplies Fatty Acids

Adipose Tissue Store Glucose

Adipose tissue, which consists of adipocytes (fat cells) (Fig. 23-16), is amorphous and widely distributed in the body under the skin, around the deep blood vessels, and in the abdominal cavity. It typically makes up about 15 of the mass of a young adult human, with approximately 65 of this mass in the form of triacylglycerols. Adipocytes are metabolically very active, responding quickly to hormonal stimuli in a metabolic interplay with the liver, skeletal muscles, and the heart.

Human brains became larger

A clue to the answer is provided by brain chemistry. The human brain is a fat-rich organ. About 60 percent of its structural material is made up of lipids, most of them long-chain polyunsaturated omega-3 and omega-6 fatty acids. Humans must consume omega fatty acids in their diet because the body cannot synthesize these molecules fast enough from the other fatty acids found in vegetables, nuts, and seeds to supply their brains. Animal brains and livers contain omega fatty acids, but fish and shellfish are by far the best sources.

Digestion And Absorption Of Lipids

Docosahexaenoic Acid Molecule

Lipids are a concentrated form of energy. They provide 30 to 40 of the daily caloric intake in the Western diet. Lipids are also essential for normal body functions, as they form part of cellular membranes and are precursors of bile acids, steroid hormones, prostaglandins, and leukotrienes. The human body is capable of synthesizing most of the lipids it requires with the exception of the essential fatty acids linoleic acid (C 18 2, an 18-carbon long fatty acid with two double bonds) and arachidonic acid (C 20 4). Both of these acids belong to the family of omega-6 fatty acids. Recently, researchers have provided convincing evidence that eicosapentaenoic acid (C 20 5) and docosahexaenoic acid (C 22 6) are also essential for the normal development of vision in newborns. Both of these acids are omega-3 fatty acids and are abundant in seafood and algae. Dietary lipids. A, A triglyceride molecule. R1, R2, and R3 belong to different fatty acids. B, A phospholipid molecule. The fatty acid...

Adipocyte Lipidbinding Protein

Utilizing a yeast two-hybrid screen of a rat adipose tissue library, it was demonstrated that HSL specifically interacts with adipocyte lipid-binding protein (ALBP or aP2 see Ref. 279 ) and the amino-terminal 300 aa of HSL has been identified as the region responsible for this interaction. This adipose-specific fatty acid-binding protein is expressed during adipocyte differentiation and makes up to 6 of cytosolic protein in mature fat cells 280 . Fatty acid-binding proteins (FABP) are abundant low-molecular-weight cytoplasmic proteins that are involved in intracel-lular trafficking and targeting as well as metabolism of FA 281 . ALBP binds FA, retinoids and other hydrophobic ligands 282 and is postulated to shuttle FA within the aqueous cytosol toward the membranes of the relevant intracellular organelles that are involved in TAG synthesis and oxidation. This transfer is believed to occur via a collision mechanism that depends on the interaction of organelle membrane phospholipids...

Mechanism and Regulation of TAG Mobilization

Cerning the functional significance of adrenoceptor-mediated increases in cAMP levels, two points should be emphasized. First, lipolytic agents generally increase the levels of cAMP far above the concentration required for maximal activation of PKA 225, 226 . Second, considerable species and tissue specificity exists with regard to the distribution of adrenoceptor subtypes. In humans, for instance, the interplay between a2- and 5-AR is important in modulating cAMP levels in adipocytes. It is now generally accepted that lipolytic response of fat cells is controlled mainly by the sympathetic nervous system and by plasma insulin levels and depends on the balance between stimulatory and inhibitory pathways. cAMP activates PKA and this kinase then phosphorylates the two main targets involved in the control of lipolysis in the adipocyte, HSL and the perilipins (Fig. 11.2). Phos-phorylation of these proteins dramatically increases lipolysis (see below). Insulin is the physiologically most...

Triacylglycerols Provide Stored Energy and Insulation

Guinea Pig Adipocytes

In most eukaryotic cells, triacylglycerols form a separate phase of microscopic, oily droplets in the aqueous cytosol, serving as depots of metabolic fuel. In vertebrates, specialized cells called adipocytes, or fat cells, store large amounts of triacylglycerols as fat droplets that nearly fill the cell (Fig. 10-3a). Triacylglycerols are also stored as oils in the seeds of many types of plants, providing energy and biosynthetic precursors during seed germination (Fig. 10-3b). Adipocytes and germinating seeds contain lipases, enzymes that catalyze the hydrolysis of stored triacylglycerols, releasing fatty acids for export to sites where they are required as fuel.

The Lack of Pancreatic Lipases or Bile Salts Can Impair Lipid Absorption

In several clinical conditions, lipid digestion and absorption are impaired, resulting in the malabsorption of lipids and other nutrients and fatty stools. Abnormal lipid absorption can result in numerous problems because the body requires certain fatty acids (e.g., linoleic and arachidonic acid, precursors of prostaglandins) to function normally. These are called essential fatty acids because the human body cannot synthesize them and is, therefore, totally dependent on the diet to supply them. Recent studies suggest that the human body may also require omega-3 fatty acids in the diet during development. These include linolenic, docosahexaenoic, and eicosapentaenoic acids. Linolenic acid is abundant in plants, and docosahexaenoic and eicos-apentaenoic acids are abundant in fish. Docosahexaenoic acid is an important fatty acid present in the retina and other parts of the brain.

Triacylglycerols In Animals And Plants

Triacylglycerols Microscopic Picture

Although adipose tissue contains many types of cells, the ones responsible for fat storage are the adipocytes (Fig. 3.2), which are bound together with connective tissue and supplied by an extensive network of blood vessels. Adipocytes are unusual in being able to expand to many times their original size by increasing their content of stored fat. When the fat content of the diet is low, fat cells can synthesize their lipid de novo from glucose, which is transported into the cell from the bloodstream (Section 3.4). When fat makes a large contribution to dietary energy, the adipocytes can take in fat from circulating lipoproteins. This involves hydrolytic breakdown of the TAG in the lipoproteins and release of fatty acids catalysed by the enzyme lipoprotein lipase (Sections 3.5.2 and 5.2.5). The fatty acids are transported into the cell and incorporated back into TAG (Section 3.4).

Malnutrition and Reproduction

The precise nature of the biochemical pathways that connect these two body systems that are essential for survival is not known. It is generally believed that the regulatory signals that modulate hypothalamic GnRH secretion are mediated through leptin and neuropeptide Y (29,31-34). Leptin, the product of the obesity (ob) gene, is a circulating hormone secreted by fat cells that acts centrally to regulate the activity of CNS effector systems that maintain energy balance (35). Leptin stimulates LH secretion by activation of the nitric oxide synthase (NOS) in gonadotropes (34). Leptin inhibits neuropeptide Y secretion, which has a tonic inhibitory effect on both leptin and GnRH secretion. Leptin also stimulates nitric oxide production in the mediobasal hypothalamus nitric oxide stimulates GnRH secretion by the hypothalamic GnRH-secreting neurons. Therefore, the net effect of leptin action is stimulation of hypothalamic GnRH secretion (31,33,34).

Lipoproteins The good the bad and the ugly

In the intestine, bile solves the problem of processing hy-drophobic fats in an aqueous medium. The transport of fats in the circulatory system presents the same problem, and lipopro-teins are the solution. A lipoprotein is a particle made up of a core of fat and cholesterol and a covering of protein that makes it water-soluble. The largest lipoprotein particles in the bloodstream are the chylomicrons produced by the mucosal cells of the intestine (see Figure 50.15). As the chylomicrons circulate through the liver and through adipose (fat) tissue throughout the body, receptors on the capillary walls recognize their protein coats, and lipases begin to hydrolyze the fats, which are then absorbed into liver or fat cells. Thus, the protein coat of the lipoprotein both makes it water-soluble and serves as an address that directs it to a specific tissue. Very-low-density lipoproteins (VLDL) contain mostly triglyceride fats, which they transport to fat cells in tissues around the body.

Decreasing heat loss is important for life in the cold

41.15 Brown Fat In many mammals, specialized brown fat tissue produces heat.When viewed through a microscope at similar magnifications, we see that white fat cells (left) are simple droplets of lipid with few organelles and limited blood supply, while brown fat cells (right) are packed with mitochondria and richly supplied with blood. 41.15 Brown Fat In many mammals, specialized brown fat tissue produces heat.When viewed through a microscope at similar magnifications, we see that white fat cells (left) are simple droplets of lipid with few organelles and limited blood supply, while brown fat cells (right) are packed with mitochondria and richly supplied with blood.

Cancer cells differ from their normal counterparts

Benign tumors resemble the tissue they came from, grow slowly, and remain localized where they develop. A lipoma, for example, is a benign tumor of fat cells that may arise in the armpit and remain there. Benign tumors are not cancers, but they must be removed if they impinge on an important organ, such as the brain.

Molecular Mechanisms

Centrations and biological responses of these second messengers. PDEs constitute a group of structurally related enzymes that belong to at least nine related gene families (PDE1-9), which differ in their primary structures, affinities for cAMP and cGMP, responses to specific effectors, and sensitivity for inhibitors and regulatory mechanisms 349, 350 . Two PDEs (PDE3 and PDE4) have high affinity for cAMP and are present in fat cells 351 . PDE3 can be distinguished from PDE4 by its high affinity for both cAMP (low Km) and cGMP (which down-regulates PDE3 activity) and is associated with the ER membrane 352 . Activation of PDE3 but not PDE4 plays a role in the antilipolytic effect of insulin in vivo in human fat tissue 353, 354 . Two distinct PDE3 subfamilies, PDE3A and PDE3B, products of distinct but related genes, have been identified, of which PDE3B is expressed in adipocytes 347, 348, 352 . The importance of PDE3 as an upstream regulator of HSL activity in insulin's antilipolytic...

Differences in Regulation of TAG Storage and Mobilization between Visceral and Subcutaneous Adipocytes

Tab. 11.2 Differences in the regulation ofTAG mobilization and storage between fat cells from visceral (vAT) and subcutaneous adipose tissue (scAT). The extent of some of these differences depends on the adipocyte hyperplasie (total fat mass) and hypertrophy as well as on the sex. Adapted from Ref. 499 with modifications (see 449 for references).

Spacelift

The name spacelift was chosen by Prof. Mang and protected by patent (German Patent Office, Patent and Logogram No 303 23891), as three-dimensional fat droplets of 0.1-0.3 mm are injected via the purified autologous fat cells into the space between the cutaneous and adipose tissue of the face, virtually as if in a honeycomb. As these fat droplets are not injected in a bolus dose but by using microinjections, they do not die but retain a vascular association and are transformed into fibroblasts, or rather connective tissue cells, and thus stabilize the aging process. Fat cells are thus injected into the space between the cutaneous and adipose tissue, particularly at those sites where the collagen and elastin fibers break down with age, i.e., in the nasolabial, mouth, forehead, lateral eye, and cheek regions.

Obesity

Also, central obesity is associated with increased PAI-1 levels, increased fibrinogen levels, increased blood viscosity, and hypertension. It is also associated with increased uric acid levels through increased platelet aggregation and adhesion, increased blood viscosity, and propensity to coagulation (11). In a cross-sectional study, central fat mass in elderly women is associated with atherogenic tendencies and peripheral fat mass exhibits an independent dominant antiatherogenic effect (114). Fat cells from people with central adiposity have greater metabolic activity compared to normal cells. This is exemplified by an increase in lipolysis and release of free fatty acids (FFA) that may interfere with insulin clearance and exacerbate hypertriglyceridemia (115). Moreover, plasma insulin concentration inversely correlates with HDL-C and directly correlates with TG concentrations in plasma (116).

Cannabis

The peak intoxication from smoking cannabis occurs after 10-30 minutes. THC and its metabolites accumulate in fat cells and have a half-life of approximately 50 hours (Franklin and Frances 1999). In intoxication, behavioral changes include a heightened sensitivity to external stimuli, de-realization, impaired motor skills, increased reaction time, and euphoria. Panic attacks can also be seen in inexperienced users. The drug is usually smoked, but users may ingest orally (e.g., hashish brownies). Psychosis can also occur during the intoxication period, evidenced by transient paranoid ideation and, rarely, frank hallucinations. Subjective reported effects of acute cannabis intoxication in individuals with schizophrenia include a decrease in anxiety and depression and an increase in suspiciousness (Dixon et al. 1990). In addition, chronic heavy cannabis use can result in an amo-tivational syndrome that is described as passivity, decreased drive, diminished goal-directed activity,...

Biguanides

Metformin (Glucophage), currently the only biguanide, acts by reducing hepatic glucose production and increasing insulin sensitivity in muscle and fat cells. The liver normally releases glucose by detecting the level of circulating insulin. When insulin levels are high, glucose is available in the blood, and the liver produces little or no glucose. When insulin levels are low, there is little circulating glucose, so the liver produces more glucose. In type 2 diabetes, the liver may not detect levels of glucose in the blood and, instead of regulating glucose production, releases glucose despite blood sugar levels.

Perilipin

Recently, Arner and coworkers investigated the amount of perilipin protein and lipolysis rates in human subcutaneous adipocytes of non-obese and obese women 523 . A polymorphism in intron 6 (rs891460 A G) in the perilipin gene seems to be associated with a 50 decrease in perilipin expression and increased basal lipolysis (AA vs. GG carriers) in adipocytes of the obese women, which in subjects matched for body mass index and adipocyte volume was inversely correlated with the plasma concentrations of NEFA and glycerol and thus may contribute to the development of insulin resistance. Furthermore, they found two- to four-fold increases in noradrenaline-induced lipolysis 523 . These data also reinforce the role of perilipin for the regulation of lipolysis in human fat cells.

Lipoma

Hand Lipoma

Lipomas are typically soft and lobular and vary from pale yellow to orange in appearance with a thin membrane surrounding the lesion. Lipomas are benign tumors that consist of mature fat cells (Fig. 85 1). This tumor commonly occurs in patients in their third to eighth decade often noted by the patients because of cosmetic concerns. Rare in the hand, they occur more frequently in the proximal upper extremity as an asymptomatic mass. When they do occur in the hand, they are usually large

TAG in Adipose Cells

Dgat1 Adipose Tissue

Adipocytes, which vary enormously in size (20-200 m in diameter), are embedded in a connective tissue matrix and are uniquely adapted to store and mobilize energy as TAG and NEFA glycerol, respectively. Surplus energy is assimilated by fat cells and stored as TAG in LD. To accommodate the TAG, adipocytes can change their diameter up to 20-fold and their volumes by several hundred-fold. Because 90 of the cell volume is constituted by LD(s), the nucleus and the thin cytoplasm rim are pushed to the periphery of the adipocytes. WAT is actively involved in cell function regulation through a complex network of endocrine, para-crine and autocrine signals that influence the response of many tissues, including hypothalamus, pancreas, liver, skeletal muscle and others. Until recently, adipo-cytes were seen as passive tissues for the storage of excess energy as TAG 118 . However, they clearly act as endocrine secretory cells 118, 119 , releasing in constitutive or regulated fashion several...

Expression of HSL

The expression of HSL protein and mRNA levels are lower in subcutaneous fat stores compared with internal (visceral, omental) fat depots in the rat 288 , suggesting a possible basis for the differences in the rate of lipolysis among various fat depots. In contrast, subcutaneous fat in humans has a higher HSL mRNA expression and HSL activity than omental fat 293 . Human subcutaneous fat cells are larger and there is a positive correlation between fat cell size and HSL expression 293 . When controlled for adipocyte cell size, the amount of HSL protein and HSL mRNA levels in subcutaneous adipocytes show a strong correlation with maximum lipolytic activity 294 .

Reproductive System

Face is made of dead cells that it sheds from the body. The sweat glands excrete waste and cool the body through evaporation of fluid droplets the blood vessels of the dermis supplement temperature regulation by contracting to preserve body heat and expanding to dissipate it. Separate kinds of receptors convey pressure, temperature, and pain. Fat cells in the dermis insulate the body, and oil glands lubricate the epidermis.

Mesenchymal tissues

Mesenchymal tissue may be present in the form of loose or dense connective tissue, cartilage, smooth and striated muscle cells, fat cells and occasionally bone. Cartilage is most readily recognized as it occurs in the form of discrete aggregates of chondroid cells surrounded by hyaline matrix (Figures 13.1 and 13.2). Such foci of cartilage-nous differentiation are usually distributed at random and may be adjacent to other mesenchymal derivatives, ectodermal derivatives such as neural tissue or choroid plexus, or endodermal derivatives such as mucin-secreting glands.

Mode of Action

The effect of acipimox on adipose tissue lipolysis has been examined under three experimental conditions 443 . Firstly, in the presence of high levels of the nonselective 5-AR agonist isoproterenol, secondly in the presence of low levels of adenosine deaminase (ADA), which when used alone have a minimal effect on basal lipolysis, yet when combined with sub-maximal concentrations of isoproterenol, substantially facilitate the lipolytic response. Thirdly, acipimox was examined in the presence of high levels of ADA. Fat cells produce adenosine from cAMP via consecutive action of PDE and 5'-nucleotidase which upon release into the medium act at specific AR to inhibit AC 444 , this inhibitory effect being mediated by the GTP-dependent 445 , pertussis toxin-sensitive 446 regulatory protein, Gi. High levels of ADA, by converting the endogenous adenosine into inosine, relieve the inhibition of AC, which results in the observed increase in basal lipolysis. The data show that acipimox has only...

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