Surgical remodeling of the silhouette by aspiration lipolysis or selective lipectomy

The author, a pioneer in originating the technique of suction lipectomy, discusses in detail the pathophysiology of the fat cell and fat metabolism. In addition, he describes the surgical means by which, since 1977, he has popularized this innovative new approach to the treatment of unsightly fat deposits in many sites in the body, including the thighs, buttocks, abdomen, hips, arms, ankles, breasts, and submental regions.     

Beta-blockade and lipolysis during endurance exercise

Summary Inhibition of adipose tissue lipolysis may be involved in the impairment of endurance capacity after administration of a -adrenoceptor blocker. During endurance exercise, no significant decrease in plasma glycerol and free fatty acid (NEFA) concentrations after -adrenoceptor blockade is found. However, the levels during recovery from exhaustion are lower after -adrenoceptor blockade. This study was designed to investigate whether the lower levels after exercise are due to -adrenoceptor blockade or to the shorter time to exhaustion after administration of a -adrenoceptor blocker.In a single-blind study, 11 well-trained male subjects (age 23 (0.9) y) performed a cycle ergometer test at 70% W_max until exhaustion 2 h after intake of 80 mg propranolol. One week later, the test was repeated after intake of placebo and was stopped at the time of exhaustion in the previous test. Average exercise time was 24 min. During exercise plasma glucose was lower, whereas plasma lactate and the respiratory exchange ratio were significantly higher when the subjects were on propranolol. Glycerol and NEFA concentrations during exercise were not significantly different between the two conditions. Despite an identical exercise time, glycerol and NEFA concentrations during recovery were significantly lower after propranol treatment.In conclusion, lipolysis is inhibited during exercise after propranolol, probably causing a shift from fat to carbohydrate combustion.     

H3 receptor-mediated inhibition of noradrenaline release: an investigation into the involvement of Ca2+ and K+ ions,G protein and adenylate cyclase

The effects of ₂-adrenoceptor agonists (dexmedetomidine, oxymetazoline), alone or in combination with various -adrenoceptor subtype-selective antagonists (CH-38083, idazoxan, WB4101, BRL44408, ARC-239, prazosin), on noradrenaline- and isoprenaline-induced lipolysis were investigated in human isolated abdominal subcutaneous fat cells. The rank order of potency of antagonists in preventing dexmedetomidine- and oxymetazoline-evoked suppression of isoprenaline-induced lipolysis was (pA₂-values): CH-38083 (7.69 and 7.48) idazoxan (7.5 and 7.41) > BRL 44408 (7.23 and 7.19) WB 4101 (7.13 and 7.12) > prazosin (5.18 and 5.17) > ARC-239 (4.72, 4.9). While CH-38083 and idazoxan, non-subtype selective ₂-adrenoceptor antagonists and BRL44408, a selective a_2A-adrenoceptor antagonist as well as WB4101 potentiated the lipolytic effect of noradrenaline, ARC-239, the selective _2B-adrenoceptor antagonist failed to affect it. In addition since the _2A-adrenoceptor selective agonist, oxymetazoline concentration dependently inhibited the lipolytic effect of isoprenaline, and WB4101 and BRL44408 (a_2A-adrenoceptor antagonists) antagonised the effect of oxymetazoline in a competitive manner, it is concluded that the a_2A-adrenoceptor subtype is involved in antilipolysis. In addition, functional evidence was obtained that there is an interaction between _2A- and -adrenoceptors located on the cell surface of adipocytes, through which locally released noradrenaline and/or circulating circulating adrenaline influence lipolysis.On leave from Institute of Medical Pharmacology, University of Pisa, Via Roma 55, I-5626 Pisa, Italy Correspondence to: E. S. Vizi at the above address     

Studies on metabolic actions of some xanthine derivatives of dopamine in the rat

Summary The lipolytic and hyperglycaemic actions of three xanthine derivatives of dopamine were studied in fed rats by determining the plasma levels of glycerol, free fatty acids and glucose. All three derivatives, 7-propyl-theophylline-dopamine, 7-(3-methyl)-propyl-theophylline-dopamine and 7-(2-methyl)-propyl-theophilline-dopamine, had a longer duration of action on lipolysis than had dopamine. These xanthine derivatives stimulated lipolysis at 10-to 100-times lower doses than dopamine and also had a greater maximal effect. Glycogenolysis was stimulated by 7-(3-methyl)- and 7-(2-methyl)-propyl-theophyllinedopamine at lower doses than by dopamine, the maximal effect, however, being smaller than that of dopamine. 7-propyl-theophylline-dopamine had practically no hyperglycaemic effect. Pretreatment with the -adrenoceptor blocking agents, phentolamine and dihydroergotamine, blocked the increase of the plasma level of glucose induced by dopamine, whereas the hyperglycaemic effect of 7-(3-methyl)-propyl-theophylline-dopamine was better antagonized by the -adrenoceptor blocking agent, propranolol. The -adrenoceptor antagonists had no clearcut effects on the lipolytic action of dopamine or its xanthine derivatives, which was, however, clearly antagonized by pretreatment with propranolol. Desipramine and reserpine, at doses which prevented the metabolic actions of tyramine, partially blocked the lipolytic and hyperglycaemic effect of dopamine, but not those of the xanthine derivatives. This suggests that the xanthine derivatives- in contrast to dopamine- do not have an indirect, tyramine-like component in their metabolic actions. Pretreatment with pargyline, an inhibitor of monoamine oxidase, strongly enhanced the metabolic effects of dopamine, but to a lesser extent the actions of its xanthine derivatives, indicating that these derivatives are more resistant to monoamine oxidase than is dopamine. The results indicate that the xanthine derivatives have metabolic effects similar to those of dopamine, but differ from dopamine in their activity and relative affinity with respect to metabolic - and -adrenoceptors and in their mechanism of action as well as in their metabolism.Deceased August 6, 1978     

Methylamine but not mafenide mimics insulin-like activity of the semicarbazide-sensitive amine oxidase-substrate benzylamine on glucose tolerance and on human adipocyte metabolism

It has been reported that benzylamine reduces blood glucose in rabbits, stimulates hexose uptake, and inhibits lipolysis in mouse, rabbit, and human adipocytes. In the presence of vanadate, benzylamine is also able to improve glucose disposal in normoglycaemic and diabetic rats. Such insulin-mimicking properties are the consequence of hydrogen peroxide production during benzylamine oxidation by semicarbazide-sensitive amine oxidase (SSAO). The aim of the study was to determine whether other SSAO-substrates could share such potential antidiabetic properties. Thus, mafenide, a synthetic antimicrobial sulfonamide structurally related to benzylamine, and which has been recently reported to interact with SSAO, was tested in the above mentioned models, in parallel with methylamine, a proposed endogenous SSAO-substrate. All tested amines stimulated glucose uptake and inhibited lipolysis in rat and mouse fat cells. Methylamine and benzylamine, but not mafenide, reduced the hyperglycaemic response during a glucose tolerance test in rabbits while the three amines tested were devoid of insulin-releasing activity under both in vivo and in vitro conditions. In human adipocytes, mafenide did not stimulate glucose transport since it was not a high-affinity substrate for SSAO and generated less hydrogen peroxide than benzylamine or methylamine. Therefore, mafenide could not be considered as an antidiabetic drug despite being oxidized and exhibiting insulin-mimicking effects in rat and mouse adipocytes. By contrast, the endogenous substrate methylamine improved glucose utilization in all in vitro and in vivo models, leading to consider novel SSAO substrates as drugs with potential anti-hyperglycaemic properties.     

In vitro and in vivo correlation for lipid-based formulations: Current status and future perspectives

Lipid-based formulations (LBFs) have demonstrated a great potential in enhancing the oral absorption of poorly water-soluble drugs. However, construction of in vitro and in vivo correlations (IVIVCs) for LBFs is quite challenging, owing to a complex in vivo processing of these formulations. In this paper, we start with a brief introduction on the gastrointestinal digestion of lipid/LBFs and its relation to enhanced oral drug absorption; based on the concept of IVIVCs, the current status of in vitro models to establish IVIVCs for LBFs is reviewed, while future perspectives in this field are discussed. In vitro tests, which facilitate the understanding and prediction of the in vivo performance of solid dosage forms, frequently fail to mimic the in vivo processing of LBFs, leading to inconsistent results. In vitro digestion models, which more closely simulate gastrointestinal physiology, are a more promising option. Despite some successes in IVIVC modeling, the accuracy and consistency of these models are yet to be validated, particularly for human data. A reliable IVIVC model can not only reduce the risk, time, and cost of formulation development but can also contribute to the formulation design and optimization, thus promoting the clinical translation of LBFs.     

The effect of exercise on regional adipose tissue and splanchnic lipid metabolism in overweight Type 2 diabetic subjects

Aims/hypothesis To test the hypothesis that adipose tissue lipolysis is enhanced in patients with Type 2 diabetes mellitus, we examined the effect of exercise on regional adipose tissue lipolysis and fatty acid mobilisation and measured the acute effects of exercise on the co-ordination of adipose tissue and splanchnic lipid metabolism.Methods Abdominal, subcutaneous adipose tissue and splanchnic lipid metabolism were studied by conducting measurements of arterio-venous concentrations and regional blood flow in six overweight Type 2 diabetic subjects before, during and after exercise.Results Exercise induced an increase in adipose tissue lipolysis and fatty acid release. However, the increase in adipose tissue blood flow was small, limiting fatty acid mobilisation from this tissue. Some of the fatty acids were released in excess in the post-exercise phase. The splanchnic fatty acid uptake was unchanged during the experiment but splanchnic ketogenesis increased in the post-exercise phase. The arterial glucose concentration decreased during exercise and continued to decrease afterwards, indicating an imbalance between splanchnic glucose production and whole-body glucose utilisation.Conclusions/interpretation Regional subcutaneous, abdominal adipose tissue lipolysis is no higher in patients with Type 2 diabetes than in young, healthy subjects. Exercise stimulates adipose tissue lipolysis, but due to an insufficient increase in blood flow, a high fraction of the fatty acids liberated by lipolysis cannot be released to the blood. Splanchnic glucose release is smaller than whole-body glucose utilisation during exercise and post-exercise recovery.Abbreviations ICG indocyanine green - 3-OHB 3-hydroxybutyrate - TAG triacylglycerol - VO_2,max peak oxygen consumption     

α2-Heremans–Schmid glycoprotein gene polymorphisms are associated with adipocyte insulin action

Aims/hypothesis The aim of this study was to investigate the effect of single-nucleotide polymorphisms (SNPs) in the gene encoding the human ₂-Heremans–Schmid glycoprotein (AHSG) on obesity and insulin action in adipocytes.Methods We screened 24 individuals for SNPs in AHSG. Six haplotype-tagging SNPs were genotyped in 188 lean and 176 obese otherwise healthy women for whom common blood chemistry phenotypes were also available. Adipocyte lipolysis and lipogenesis phenotypes were quantified in a subset of 117 lean and 174 obese women.Results The –469T>G SNP, which is located in the 5 region of AHSG, was associated with insulin-mediated inhibition of lipolysis and stimulation of lipogenesis, as well as basal and 8-bromocyclic AMP-stimulated lipolysis. Three AHSG SNPs were associated with circulating levels of cholesterol. None of the six genotyped SNPs or inferred haplotypes were associated with BMI, calculated percent body fat, waist circumference, circulating levels of glucose or insulin, or homeostasis model assessment of insulin resistance, which was used as an estimate of in vivo insulin sensitivity.Conclusions/interpretation Our results are in agreement with a threshold model of susceptibility for insulin resistance and type 2 diabetes, in which specific genetic loci regulate intermediate molecular phenotypes. When an individuals set of susceptibility alleles at such loci exceeds a threshold, clinical disease occurs. Lipolysis in adipocytes appears to be a phenotype that is particularly sensitive to variation in AHSG.