Atrial natriuretic peptide inhibits the production of adipokines and cytokines linked to inflammation and insulin resistance in human subcutaneous adipose tissue

Aims/hypothesis Increased adipose tissue secretion of adipokines and cytokines has been implicated in the chronic low-grade inflammation state and insulin resistance associated with obesity. We tested here whether the cardiovascular and metabolic hormone atrial natriuretic peptide (ANP) was able to modulate adipose tissue secretion of several adipokines (derived from adipocytes) and cytokines (derived from adipose tissue macrophages). Subjects and methods We used protein array to measure the secretion of adipokines and cytokines after a 24-h culture of human subcutaneous adipose tissue pieces treated or not with a physiological concentration of ANP. The effect of ANP on protein secretion was also directly studied on isolated adipocytes and macrophages. Gene expression was measured by real-time RT-quantitative PCR. Results ANP decreased the secretion of the pro-inflammatory cytokines IL-6 and TNF-α, of several chemokines, and of the adipokines leptin and retinol-binding protein-4 (RBP-4). The secretion of the anti-inflammatory molecules IL-10 and adiponectin remained unaffected. The cytokines were mainly expressed in macrophages that expressed all components of the ANP-dependent signalling pathway. The adipokines, leptin, adiponectin and RBP-4 were specifically expressed in mature adipocytes. ANP directly inhibited the secretion of IL-6 and monocyte chemoattractant protein-1 by macrophages. The inhibitory effects of ANP on leptin and growth-related oncogene-α secretions were not seen under selective hormone-sensitive lipase inhibition. Conclusions/interpretation We suggest that ANP, either by direct action on adipocytes and macrophages or through activation of adipocyte hormone-sensitive lipase, inhibits the secretion of factors involved in inflammation and insulin resistance.     

脂肪组织甘油三酯脂肪酶的研究进展

脂肪组织甘油三酯脂肪酶(ATGL)是新近发现的启动脂肪动员的另一关键酶,其主要催化脂肪组织中甘油三酯生成甘油二酯,与长期认为的经典限速酶激素敏感性脂肪酶(HSL)在脂肪分解途径中共同承担着重要作用.鉴于ATGL与脂肪分解密切相关,并在脂肪代谢紊乱性疾病中发挥着重要的作用,本文就ATGL的研究进展及与脂肪分解、肥胖和2型糖尿病等脂代谢紊乱性疾病的关系作一综述.     

Family history of diabetes is associated with enhanced adipose lipolysis: Evidence for the implication of epigenetic factors

Aims

Type 2 diabetes is associated with insulin resistance, adipose hypertrophy and increased lipolysis. The heritability of these traits has been determined by associating them with a family history of diabetes.

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     

Age-related effects of fasting on ketone body production during lipolysis in rats

Objective

The age-related effects of fasting on lipolysis, the production of ketone bodies, and plasma insulin levels were studied in male 3-, 8-, and 32-week-old Sprague–Dawley rats.

Methods

The rats were divided into fasting and control groups. The 3-, 8- and 32-week-old rats tolerated fasting for 2, 5, and 12 days, respectively.

Results

Fasting markedly reduced the weights of perirenal and periepididymal white adipose tissues in rats in the three age groups. The mean rates of reduction in both these adipose tissue weights during fasting periods were higher in the order of 3 > 8 > 32-week-old rats. Fasting transiently increased plasma free fatty acid (FFA), total ketone body, β-hydroxybutyrate, and acetoacetate concentrations in the rats in the three age groups. However, plasma FFA, total ketone body, β-hydroxybutyrate, and acetoacetate concentrations in the 3-week-old rats reached maximal peak within 2 days after the onset of fasting, although these concentrations in the 8- and 32-week-old rats took more than 2 days to reach the maximal peak. By contrast, the augmentation of plasma FFA, total ketone body, β-hydroxybutyrate, and acetoacetate concentrations in the rats in the three age groups had declined at the end of each experimental period. Thus, the capacity for fat mobilization was associated with tolerance to fasting. Plasma insulin concentrations in the rats in the three age groups were dramatically reduced during fasting periods, although basal levels of insulin were higher in the order of 32 > 8 > 3 week-old rats.

Conclusion

These results suggest that differences in fat metabolism patterns among rats in the three age groups during prolonged fasting were partly reflected the metabolic turnover rates, plasma insulin levels, and amounts of fat storage.     

Diabetogenic activity of the anterior pituitary (a progress report)

Summary The exact nature of the diabetogenic activity of the anterior pituitary gland remains a mystery. While growth hormone (GH) fractions clearly can produce a diabetogenic effect, there is increasing evidence that GH itself does not exert this effect. Several new theories that purport to explain the nature of diabetogenic activity are discussed. The current evidence supports the view that the activity is the result of a GH fragment or some other closely related protein such as the one (‘diabetogenic protein’) first described byLouis andConn. A progress report of the research on this new ‘diabetogenic protein’ is given.     

The beneficial effect of glycerophosphocholine to local fat accumulation: a comparative study with phosphatidylcholine and aminophylline

Injection lipolysis or mesotherapy gained popularity for local fat dissolve as an alternative to surgical liposuction. Phosphatidylcholine (PPC) and aminophylline (AMPL) are commonly used compounds for mesotherapy, but their efficacy and safety as lipolytic agents have been controversial. Glycerophosphocholine (GPC) is a choline precursor structurally similar to PPC, and thus introduced in aesthetics as an alternative for PPC. This study aimed to evaluate the effects of GPC on adipocytes differentiation and lipolysis and compared those effects with PPC and AMPL using in vitro and in vivo models. Adipogenesis in 3T3-L1 was measured by Oil Red O staining. Lipolysis was assessed by measuring the amount of glycerol released in the culture media. To evaluate the lipolytic activity of GPC on a physiological condition, GPC was subcutaneously injected to one side of inguinal fat pads for 3 days. Lipolytic activity of GPC was assessed by hematoxylin and eosin staining in adipose tissue. GPC significantly suppressed adipocyte differentiation of 3T3-L1 in a concentration-dependent manner (22.3% inhibition at 4 mM of GPC compared to control). Moreover, when lipolysis was assessed by glycerol release in 3T3-L1 adipocytes, 6 mM of GPC stimulated glycerol release by two-fold over control. Subcutaneous injection of GPC into the inguinal fat pad of mice significantly reduced the mass of fat pad and the size of adipocytes of injected site, and these effects of GPC were more prominent over PPC and AMPL. Taken together, these results suggest that GPC is the potential therapeutic agent as a local fat reducer.     

Differences in functional cyclic AMP compartments mediating lepolysis by isoprenaline and BRL 37344 in four adipocyte types

Triglyceride mobilization and adenylyl cyclase activation in adipocytes from Wistar rats, lean Zucker (Fa/?) rats, obese Zucker (fa/fa) rats and humans were investigated in concentration-response studies with (−)-isoprenaline and the atypical β₃-adrenoceptor selective agonist BRL 37344. Maximum FFA production by both agonists was identical in Wistar rat and lean Zucker rat adipocytes, while obese Zucker rat adipocytes and human adipocytes produced significantly less FFA, especially with BRL 37344. Maximum adenylyl cyclase activation by (−)-isoprenaline was similar for all types of adipocyte ghosts, whereas BRL 37344 was a partial agonist in all cases with the lowest intrinsic activity in human adipocytes. For (−)-isoprenaline the relationship between cAMP and lipolysis was steepest with Wistar rat adipocytes, followed by human and lean Zucker rat adipocytes, while obese Zucker rat cells showed a shallow relationship. For BRL 37344, the relationship was very steep and similar for all four adipocyte types, despite the marked differences in maximal lipolysis and cyclic AMP production. The results strongly argue in favour of cyclic AMP compartmentalization, the activity ratio between the functional and the non-functional compartment being least favourable in obese Zucker rat adipocytes. The atypical β₃-adrenoceptor agonist BRL 37344 very efficiently directs the generated cyclic AMP into the functional compartment in all four adipocytes types investigated.     

Optimum vacuum pressures for lipolysis

The author presents a method to test the adequacy of any suction machine pump used in lipolysis surgery, regardless of the altitude and/or sea level of the operating room physical conditions. Surgeons can, therefore, subject any vacuum pump to a vaporization test and thereby ensure its adequacy for lipolysis techniques.