Adipose tissue-produced hormones significantly affect the metabolism of lipids and carbohydrates as well as numerous other processes in human body. It is generally accepted that endocrine dysfunction of adipose tissue may represent one of the causal links between obesity and insulin resistance/diabetes. Epidemiological studies underlined that obesity represents a significant risk factor for the development of cancer, although the exact mechanism of this relationship remains to be determined. Multiple recent studies have indicated that some of adipose tissue-derived hormones may significantly influence the growth and proliferation of tumorous stroma and malignant cells within. Here we review current knowledge about possible relationship of leptin and adiponectin to the etiopathogenesis of different malignant tumors. Most of the studies indicated that while leptin may potentiate the growth of cancer cells in vitro, adiponectin appears to have an opposite effect. Further studies are necessary to decide whether obesity-induced endocrine dysfunction of adipose tissue can directly influence carcinogenesis in different tissues and organs.
Adipose tissue is a hormonally active tissue, producing adipocytokines which may influence activity of other tissues. Adiponectin, abundantly present in the plasma increases insulin sensitivity by stimulating fatty acid oxidation, decreases plasma triglycerides and improves glucose metabolism. Adiponectin levels are inversely related to the degree of adiposity. Anorexia nervosa and type 1 diabetes are associated with increased plasma adiponectin levels and higher insulin sensitivity. Decreased plasma adiponectin levels were reported in insulin-resistant states, such as obesity and type 2 diabetes and in patients with coronary artery disease.Activity of adiponectin is associated with leptin, resistin and with steroid and thyroid hormones, glucocorticoids, NO and others.
Adiponectin suppresses expression of extracellular matrix adhesive proteins in endothelial cells and atherosclerosis potentiating cytokines. Anti-atherogenic and anti-inflammatory properties of adiponectin and the ability to stimulate insulin sensitivity have made adiponectin an important object for physiological and pathophysiological studies with the aim of potential therapeutic applications.
Experimental hypothermia caused extensive changes in the number of both classes of insulin receptors in different rat tissues. In the liver, the number of high affinity insulin receptors (HAIRs) decreased by 50 % (from 25.3 to 12.6 fmol/mg membrane protein), whereas number of low affinity insulin receptors (LAIRs) was almost unchanged in comparison to normothermic animals (5.63 and 4.39 pmol/mg, respectively). In the adipose tissue, number of both classes was reduced - HAIRs by 81 % (from 24.0 to 4.50 fmol/mg) and LAIRs by 92 % (from 16.0 to 1.29 pmol/mg). In the skeletal muscle, capacity of HAIRs was not changed (16.2 and 19.3 fmol/mg in normo- and hypothermic animals, respectively), whereas number of LAIRs increased by 150 % (from 6.65 to 16.6 pmol/mg). Hypothermic rats also showed lower amount (by 85 %) of LAIRs in the heart muscle (9.37 and 1.43 pmol/mg in control and experimental animals, respectively). Simultaneously, no significant changes were found in HAIRs (16.3 and 11.9 fmol/mg, respectively) and LAIRs (4.43 and 3.88 pmol/mg, respectively) in the brain. These differences in insulin receptors responses to hypothermia may reflect different physiological role of insulin in the regulation of target cell metabolism and/or the differences in tissue distribution of the insulin receptor isoforms., T. Torlinska, M. Perz, E. Madry, T. Hryniewiecki, K. W. Nowak, P. Mackowiak., and Obsahuje bibliografii
The present investigation was directed to study the effect of in vitro or ex vivo NO donors, sodium nitroprusside and molsidomine, using isolated sliced adipose tissue or in the form of immobilized and perfused adipocytes on the basal and isoprenaline-stimulated lipolysis. The results demonstrated that 1) in vitro application of sodium nitroprusside to perfused adipocytes or molsidomine to sliced adipose tissues affects isoprenaline-induced lipolysis in two ways, an increase in lipolysis at low isoprenaline concentrations (which means the sensitization of adipose tissues to adrenergic effect by NO) and decreased adrenergic agonist-stimulated lipolysis at higher concentration of isoprenaline (a decrease in the maximum lipolytic effect of isoprenaline), 2) low concentrations of molsidomine alone induced lipolysis from adipose tissue which attained more than 60 % of that by isoprenaline (pD2 value for molsidomine = 11.2, while pD2 for isoprenaline = 8.17) while sodium nitroprusside did not affect the basal lipolysis significantly, 3) in vivo administration of molsidomine for 2 days reduced the maximum lipolytic effect of isoprenaline and (only non-significantly) increased the sensitivity to low doses of isoprenaline. In conclusion the present data demonstrate that NO plays an important role in adrenergic lipolysis in adipose tissues and further investigations are needed to unravel the exact role of NO in lipolysis., D. Lincová, D. Mišeková, E. Kmoníčková, N. Canová, H. Farghali., and Obsahuje bibliografii
Body fat content is controlled, at least in part, by energy charge of adipocytes. In vitro studies indicated that lipogenesis as well as lipolysis depend on cellular ATP levels. Respiratory uncoupling may, through the depression of ATP synthesis, control lipid metabolism of adipose cells. Expression of some uncoupling proteins (UCP2 and UCP5) as well as other protonophoric transporters can be detected in the adipose tissue. Expression of other UCPs (UCP1 and UCP3) can be induced by pharmacological treat
ments that reduce adiposity. A negative correlation between the accumulation of fat and the expression of UCP2 in adipocytes was also found. Ectopic expression of UCP1 in the white fat of aP2-Ucp1 transgenic mice mitigated obesity induced by genetic or dietary factors. In these mice, changes in lipid metabolism of adipocytes were associated with the depression of intracellular energy charge. Recent data show that
AMP-activated protein kinase may be involved in the complex changes elicited by respiratory uncoupling in adipocytes. Changes in energy metabolism of adipose tissue may mediate effects of treatments directed against adiposity, dyslipidemia, and insulin resistance.
Insulin resistance (IR) is the result of long-lasting positive energy balance and the imbalance between the uptake of energy rich substrates (glucose, lipids) and energy output. The defects in the metabolism of glucose in IR and type 2 diabetes are closely associated with the disturbances in the metabolism of lipids. In this review, we have summarized the evidence indicating that one of the important mechanisms underlying the development of IR is the impaired ability of skeletal muscle to oxidize fatty acids as a consequence of elevated glucose oxidation in the situation of hyperglycemia and hyperinsulinemia and the impaired ability to switch easily between glucose and fat oxidation in response to homeostatic signals. The decreased fat oxidation results into the accumulation of intermediates of fatty acid metabolism that are supposed to interfere with the insulin signaling cascade and in consequence negatively influence the glucose utilization. Pathologically elevated fatty acid concentration in serum is now accepted as an important risk factor leading to IR. Adipose tissue plays a crucial role in the regulation of fatty acid homeostasis. The adipose tissue may be the primary site where the early metabolic disturbances leading to the development of IR take place and the development of IR in other tissues follows. In this review we present recent evidence of mutual interaction between
skeletal muscle and adipose tissue in the establishment of IR and type 2 diabetes.
The present study was designed to measure interstitial levels of norepinephrine-regulating lipolysis (NE) in subcutaneous abdominal adipose tissue of anorexia nervosa (AN) patients and control subjects under basal conditions and after the local administration of an inhibitor of NE re-uptake, maprotiline. In vivo microdialysis technique was used to assess subcutaneous adipose NE levels in five women with AN (body mass index 14.62±0.47 kg/m2) and six age-matched controls (22.1±0.52 kg/m2). NE was assayed using high performance liquid chromatography with electrochemical detection after batch alumina extraction. Measured basal adipose tissue NE levels reflecting its interstitial levels were significantly increased in AN patients compared to the controls (106.0±20.9 vs. 40.0±5.0 pg/ml). The local maprotiline administration resulted in a significant increase in adipose tissue NE levels (AN patients: 440.0±28.6 vs. 202.0±33.0 pg/ml in the controls) in both groups. Markedly increased subcutaneous abdominal adipose tissue NE levels in AN patients compared to control subjects reflect increased sympathetic nervous system activity but not altered membrane noradrenergic transporter system in anorexia nervosa patients.
Peroxisome proliferator-activated receptors (PPAR) belong to the nuclear receptor superfamily of ligand-activated transcription factors. PPAR-α
, first of its three subtypes (α, β, γ) has traditionally been considered an important regulator of lipid metabolism while its role in the regulation of insulin sensitivity has not been recognized until recently. Here we summarize the experimental and clinical studies focusing on the role of PPAR-α in the regulation of insulin sensitivity. In most of the experimental studies the activation of PPAR-α in rodents leads to improvement of insulin sensitivity by multiple mechanisms including improvement of insulin signaling due to a decrease of ectopic lipids in
non-adipose tissues and decrease of circulating fatty acids and triglycerides
. In contrast, the effect of PPAR-α agonist in humans is much less pronounced probably due to a lower expression of PPAR-α relative to rodents and possibly other mechanisms. Further clinical studies using more potent PPAR-α agonists on a larger population need to be performed to
evaluate the possible role of PPAR-α in the regulation of insulin sensitivity in humans.