Evaluation of tissue thermal effects from 1064/1320-nm laser-assisted lipolysis and its clinical implications

Liposuction is a standard for removing fat. Recently developed, laser lipolysis can be used to simultaneously remove unwanted fat and tighten skin. Laser lipolysis is accomplished with single or multiple sequential wavelengths. Development of an optimal method requires detailed understanding of tissue heating for the wavelengths employed. This study systematically evaluates tissue heating for superficial and deep laser lipolysis using three approaches, and correlates temperature rise with histology changes, defining appropriate system parameters. Two individuals scheduled for abdominoplasty had laser testing on healthy abdominal skin scheduled for excision. Each treatment was applied to 3×3 cm squares with various laser parameters. Treatment was conducted in the fatty layer for lipolysis and subdermally for skin tightening. Individual squares were treated with SmartLipo (Cynosure, Inc. Westford, MA, USA) using 1064 nm, 1320 nm, or MultiPlex (1064 nm/1320 nm) with laser doses of 8.3 to 333 J/cm². Exposures were applied at 3–5 mm or ～20 mm depth below the skin surface. Skin temperatures at the surface and at depths of 5 mm to 37 mm were recorded immediately post-treatment for each exposure. Treated tissue was excised and evaluated for thermal injury using H&E and transmission polarization microscopy. Histology was correlated to tissue temperature to determine appropriate treatment limits. Superficial treatment with surface temperatures exceeding 47°C (50°C and 55°C at 5 mm depth) typically caused epidermal and dermal injury, with blistering above 58°C. Below this threshold, focal collagen change and dermal inflammatory response were found in many samples without epidermal injury. These acute thermal effects may link to skin tightening during the healing process. Deep treatments, at up to 133 J/cm², exhibited minimal temperature rise and induced thermal effects in vessels and ligaments. Higher laser doses were associated with a significant temperature increase. In conclusion, superficial subdermal heating (within approximately 5 mm of the surface) during laser lipolysis should limit skin surface temperature to 42°C. The laser dose per surface temperature rise in treatments are 4.5 J/cm²/°C for 1320 nm, 6 J/cm²/°C for MultiPlex and 7.5 J/cm²/°C for 1064 nm. Clinical studies should be performed to validate these results.     

Reduction of subcutaneous fat and improvement in cellulite appearance by dual‐wavelength,low‐level laser energy combined with vacuum and massage

Background: This study compares the efficacy and safety of low‐level, dual‐wavelength laser energy and massage with massage alone for the reduction of subcutaneous fat in the thighs of normal women. The device was an early prototype of the FDA‐cleared SmoothShapes^TM system (Elemé Medical, Merrimack, NH, USA). Methods: The thighs of each individual (n = 102) were randomized to either laser light (dual wavelength of 650±20?nm and 915±10?nm) and massage or to massage alone (control). Individuals who completed the study (n = 74) received a mean of 14.3 treatments over 4–6 weeks. Magnetic resonance imaging (MRI) scans quantified fat pad dimensions before and after the final treatment. Results: Fat thickness decreased for the leg treated with laser‐massage by 1.19 cm² (mean) and increased by 3.82 cm² (mean) for the control leg over time. The difference was statistically significant (p<0.001). Among those who completed the study, 82.26% responded to treatment. Individuals reported looser‐fitting clothing and satisfaction with the procedure and results. Adverse effects were limited to occasional increases in urinary frequency. Conclusion: Low‐level, dual‐beam laser energy with massage appears to be safe and more efficacious than massage alone for reducing subcutaneous fat in the thighs of normal women.     

Targeting cardiac natriuretic peptides in the therapy of diabetes and obesity

Introduction: Atrial and B-type Natriuretic Peptides (NP) are cardiac hormones with potent cardiovascular and metabolic effects. They signal through the NPRA/cGMP system and are inactivated by a clearance receptor NPRC and neutral endopeptidases (NEP). Recombinant ANP and BNP are currently used as drug treatment for acute decompensated congestive heart failure. Recent literature indicate that a defective NP system is linked to obesity and predict the risk of type 2 diabetes (T2D).

Areas covered: This article reviews recent epidemiological, clinical and preclinical evidences that NP system deficiency may be causal of obesity and T2D. The molecular mechanisms of the NP pathway in several metabolic target tissues are presented. The therapeutic potential of NP in obesity and T2D is discussed.

Expert opinion: Targeting the NP pathway may offer a novel therapeutic avenue for the management of obesity and T2D. The benefit/risk of drugs increasing circulating NP levels by blocking NPRC and NEP, and/or enhancing NPRA signaling should be assessed in obese and type 2 diabetic individuals.     

杨梅素联合围脂滴蛋白对脂肪细胞脂解的影响

目的 研究杨梅素（Myric）与围脂滴蛋白（PLIN1）联合作用对3T3-L1 脂肪细胞脂解的影响。 方法 常规培养及诱导分化3T3-L1 前脂肪细胞,筛选出Myric 最佳干预浓度和时间。Myric 联合sh-RNA 干 扰载体对已诱导分化成熟的3T3-L1 脂肪细胞进行联合干预,实验共分为四组：联合干预组（Myric+sh-RNA）、 转染组（sh-RNA）、杨梅素组（Myric）和空白组。采用油红O 进行脂滴染色,观察脂滴形态;采用酶学方法 检测细胞中三酰甘油（TG）和甘油含量,了解细胞脂解情况;采用Western blot 检测脂肪细胞中PLIN1A、三 酰甘油脂肪酶（ATGL）和激素敏感性脂肪酶（HSL）的表达量。结果 以浓度为100 μmol/L 的Myric 干预 72 h 时,细胞内TG 含量最低,甘油含量最高,脂解效果最佳,与其他浓度和干预24 h 比较,差异有统计学意义 （P <0.05）。联合干预后,与Myric 组和sh-RNA 组比较,Myric+sh-RNA 组细胞内TG 含量下降,甘油含量升 高,脂滴形态变小,数量减少,差异有统计学意义（P <0.05）。同时,Myric+sh-RNA 组PLIN1A 蛋白表达量降低, ATGL 和HSL 蛋白表达量升高,差异有统计学意义（P <0.05）。结论 Myric 联合PLIN1 可以更有效降低PLIN1 表达量,提高ATGL 与HSL 的表达量,从而提高脂解效率。     

Peripheral Actions of Leptin and Its Involvement in Disease

The discovery of leptin is broadening our understanding of the mechanisms underlying neuroendocrine function. To date, most investigations have focused on the effects of leptin on food intake control and body weight homeostasis with attention primarily focused on the central effects of leptin. However, the almost ubiquitous distribution of leptin receptors in peripheral tissues provides a fertile area for investigation and a more dynamic view of leptin is starting to unfold. Thus, leptin has generated enormous interest in the interaction as well as integration between brain targets and peripheral signals. The scientific evidence supporting the direct peripheral effects of leptin on angiogenesis, wound healing, lipolysis, blood pressure homeostasis, and satiety control is reviewed.     

Increased lipolytic sensitivity to catecholamines in diabetic patients with severe autonomic neuropathy

Lipolytic sensitivity to catecholamines was studied in gluteal adipocytes from diabetic subjects with severe (n = 3), mild (n = 6) or no autonomic neuropathy (n = 8). Two of the three patients with severe autonomic neuropathy had a completely abolished plasma epinephrine response to insulin-induced hypoglycaemia, whereas the third patient showed a reduced and delayed plasma epinephrine response. Lipolytic sensitivity to isoprenaline (P less than 0.05), and to epinephrine in the presence of yohimbine (P less than 0.0001), was significantly increased in the diabetic subjects with severe autonomic neuropathy, compared to the other study groups. Moreover, the specific binding of the beta-adrenoceptor antagonist (+-)-4-(3-butylamino-2-hydroxypropoxyl)-(5.7-3H)-benzimidazole- -2-one-hydrochloride (3H-CGP) was markedly exaggerated (P less than 0.05) in the patients with severe autonomic neuropathy. These findings demonstrate that the lipolytic sensitivity to catecholamines in adipose tissue was increased only in patients with severe autonomic neuropathy and impaired epinephrine response to insulin-induced hypoglycaemia. This increased beta-adrenergic sensitivity could, at least in part, be attributed to an increased density of beta-adrenergic receptors in the adipocytes.     

Plasma kinetics of chylomicron-like emulsion in renal transplant patients receiving cyclosporin-based immunosuppression

Background: Atherosclerotic cardiovascular disease is prevalent among renal transplant patients. Increase in serum total cholesterol, low-density lipoprotein, and very low-density lipoprotein is common in those patients. Alterations in chylomicron metabolism, however, are also related to atherogenesis and were not studied in renal transplant. Hypothesis: The aim of this study was to evaluate chylomicron metabolism in renal transplant recipients receiving cyclosporin-based immunosuppression. We determined the plasma kinetics of triglyceride-rich emulsions labeled with pHjtriolein and [^l4C]cholesteryl oleate that are known to mimic the chylomicron metabolism when injected into the blood stream. Methods: Fourteen renal transplant recipients with normal renal function (10 men, 4 women, aged 40 $pL 6.1 years) and 17 age- and gender-matched healthy controls received bolus injections of the chylomicron-like emulsion. Plasma samples were then taken at regular intervals during 60 min. Disappearance curves of the labels and the respective fractional clearance rates (FCR) were calculated in order to measure lipolysis and chylomicron remnant removal from the plasma. Results: Fasting serum lipid levels did not differ in the two groups. The difference between Median FCR of [³H]triolein emulsion in renal transplant patients and that obtained in the controls (0.07 vs. 0.11 min^-1, NS) was not statistically significant. Median FCR of [¹⁴C]cholesteryl oleate also did not differ between the groups (patients: 0.044 controls: 0.046, NS). Conclusion: These results indicate that neither chylomicron lipolysis nor remnant removal are affected in stable renal transplant patients treated with cyclosporin-based immunosuppression.     

ROLE OF MEDIUM-CHAIN TRIGLYCERIDES IN FORMULAS FOR PREMATURE INFANTS

In terms of fat absorption or growth of low-birthweight infants, use of medium-chain triglycerides in formulas for premature infants conferred no advantage over that of long-chain triglycerides.     

Regulation of beta3-adrenoceptor expression in white fat cells*

Summary— Catecholamines (adrenaline and noradrenaline) stimulate adipocyte lipolysis via three beta-adrenoceptor subtypes β₁, β₂ and β₃. β₃-adrenoceptor-mediated lipolysis varies according to the species. Rodent adipocytes exhibit the strongest response to β₃ agonists while human fat cells are poorly responsive. The species-related differences can partly be explained by lower β₃-adrenoceptor mRNA levels in human adipocytes compared to rat adipocytes. Poor coupling efficiency of human adipocyte β₃-adrenoceptors cannot, however, be ruled out. The regulation of β₃-adrenoceptor gene expression has been studied in the adipocytes of the murine cell line 3T3-F442A which express high levels of β₃-adrenoceptors. Insulin and glucocorticoids down-regulate β₃-adrenoceptor expression through a trancriptional effect. The impairment of β₃-adrenoceptor gene expression in adipocytes of congenitally obese ob/ob mice could be related to the higher glucocorticoid plasma levels when compared to lean littermates although the direct involvement of glucocorticoids remains to be demonstrated. In the rat and the rabbit, the β₃-adrenergic responsiveness varies according to the anatomical location of the fat pad. There is a marked decrease in β₃-adrenergic response in rabbit retroperitoneal fat cells during ageing. cAMP modulates the β₃-adrenergic response in white adipocytes at different levels. Human β₃-adrenoceptor expression seems to be up-regulated by cAMP through an interaction with the promoter of the gene. It has been shown in cells transfected with cDNAs for the different β-adrenoceptors that the β₃-adrenoceptor is less prone to desensitization than the β₁ and β₂-subtypes. This observation is in agreement with the absence of desensitization of the β₃-adrenoceptor response in isolated rat fat cells. Continuous infusion of noradrenaline for six days into hamsters does not lead to an alteration of the β-adrenergic response. A similar treatment undertaken in the guinea pig, a species, unlike the hamster, devoid of β₃-adrenoceptor responsiveness, promoted strong desensitization of the β-adrenergic response through down-regulation of β₁- and β₂-adrenoceptors. From these observations, it could be hypothesized that the β₃-adrenoceptor, that shows a low affinity for catecholamines, is the “emergency” β-adrenoceptor which is essential under conditions of strong and sustained sympathetic nervous system activation.     

Insulin resistance in Graves'' disease: a quantitative in-vivo evaluation

Hyperthyroidism is considered to be an insulin-resistant state, but a quantitative evaluation of some action of insulin is still lacking. We performed euglycaemic clamp at about 350 and 7000 pmol l-1 plasma insulin concentration in combination with the 3H-glucose infusion in 12 patients with Graves' disease and in 12 matched controls. Fasting plasma insulin (126 +/- 6.5 vs. 77.5 +/- 5.7 pmol l-1; P less than 0.001), C-peptide (502 +/- 36 vs. 363 +/- 41 pmol l-1; P less than 0.001) and glucagon (47 +/- 3.3 vs. 33.3 +/- 3 pmol l-1; P less than 0.01) were significantly higher in hyperthyroids than in euthyroids. Basal hepatic glucose production was significantly higher in hyperthyroids than in euthyroids (18.3 +/- 1.4 vs. 9.2 +/- 0.5 mumol l-1; P less than 0.0001), and its suppression during physiological hyperinsulinaemia was only 50% in hyperthyroids. Glucose utilization and suppression of lipolysis were normally stimulated by insulin. All parameters altered during hyperthyroidism were normalized during methimazole-induced euthyroidism. We conclude that insulin resistance involves mainly glucose rather than lipid and is selective at the hepatic level.