Withaferin A Promotes White Adipose Browning and Prevents Obesity Through Sympathetic Nerve-Activated Prdm16-FATP1 Axis

The increasing prevalence of obesity has resulted in demands for the development of new effective strategies for obesity treatment. The Withaferin A (WA) shows a great potential for prevention of obesity by sensitizing leptin signaling in the hypothalamus. However, the mechanism underlying the weight- and adiposity-reducing effects of WA remains to be elucidated. Here, we report that WA treatment induced white adipose tissue (WAT) browning, elevated energy expenditure (EE), decreased respiratory exchange ratio (RER), and prevented high-fat diet (HFD)-induced obesity. The sympathetic chemical denervation dampened the WAT browning and also impeded the reduction of adiposity in WA-treated mice. WA markedly up-regulated the levels of Prdm16 and FATP1 (Slc27a1) in the inguinal WAT (iWAT), and this was blocked by sympathetic denervation. Prdm16 or FATP1 knockdown in iWAT abrogated the WAT browning-inducing effects of WA, and restored the weight gain and adiposity in WA-treated mice. Together, these findings suggest that WA induces WAT browning through the sympathetic nerve-adipose axis; and the adipocytic Prdm16-FATP1 pathway mediates the promotive effects of WA on white adipose browning.

Withaferin A Promotes White Adipose Browning and Prevents Obesity Through Sympathetic Nerve-Activated Prdm16-FATP1 Axis

The increasing prevalence of obesity has resulted in demands for the development of new effective strategies for obesity treatment. The Withaferin A (WA) shows a great potential for prevention of obesity by sensitizing leptin signaling in the hypothalamus. However, the mechanism underlying the weight- and adiposity-reducing effects of WA remains to be elucidated. Here, we report that WA treatment induced white adipose tissue (WAT) browning, elevated energy expenditure (EE), decreased respiratory exchange ratio (RER), and prevented high-fat diet (HFD)-induced obesity. The sympathetic chemical denervation dampened the WAT browning and also impeded the reduction of adiposity in WA-treated mice. WA markedly up-regulated the levels of Prdm16 and FATP1 (Slc27a1) in the inguinal WAT (iWAT), and this was blocked by sympathetic denervation. Prdm16 or FATP1 knockdown in iWAT abrogated the WAT browning-inducing effects of WA, and restored the weight gain and adiposity in WA-treated mice. Together, these findings suggest that WA induces WAT browning through the sympathetic nerve-adipose axis; and the adipocytic Prdm16-FATP1 pathway mediates the promotive effects of WA on white adipose browning.

Withaferin A promotes white adipose browning and prevents obesity through sympathetic nerve-activated Prdm16-FATP1 axis

The increasing prevalence of obesity causes demands for new strategies for obesity treatment. Withaferin A (WA) shows a great potential for obesity prevention by sensitizing leptin signaling in hypothalamus. However, the mechanism underlying weight- and adiposity-reducing effects of WA remains elusive. We report that WA induced white adipose tissue (WAT) browning, elevated energy expenditure (EE), decreased respiratory exchange ratio (RER), and prevented high-fat diet (HFD)-induced obesity. Sympathetic chemical denervation dampened WAT browning and impeded reduction of adiposity in WA-treated mice. WA up-regulated the levels of Prdm16 and FATP1 (Slc27a1) in the inguinal WAT (iWAT), and this was blocked by sympathetic denervation. Prdm16 or FATP1 knockdown in iWAT abrogated WAT browning-inducing effects of WA, and restored weight gain and adiposity in WA-treated mice. Together, these findings suggest that WA induces WAT browning through the sympathetic nerve-adipose axis; and the adipocytic Prdm16-FATP1 pathway mediates the promotive effects of WA on WAT browning.

Open Eyebrow Correction

The open brow lift is a powerful tool for facial rejuvenation of the upper third of the face which can address rhytids, upper eyelid hooding, and brow ptosis. With a history dating back over a hundred years, a variety of techniques have been described including coronal, pretrichial, mid-forehead, direct supraciliary, and transpalpebral brow lifts. These vary in terms of invasiveness and the ideal approach is determined by patient age, sex, symmetry, and anterior hairline characteristics. While endoscopic techniques became popular in the 1990s based on novelty, smaller incisions, less post-scar numbness, and a perception of less invasive nature, this technique’s popularity has diminished recently and less invasive open approaches have become more popular. Recent years have seen the numbers of all forms of brow lift become less common as neuromodulators, such as botulinum toxin, allow for chemical denervation of brow depressor muscles. This has become a truly non-invasive way to address minor forms of aging of the forehead and brow. However, for advanced cases, open brow lift remains a powerful technique which should remain in the arsenal of the plastic surgeon. This review contains 3 figures, 2 tables, and 39 references. Keywords: cosmetic surgery, facial plastic surgery, facial aging, brow ptosis, rhytids, facial nerve, supraorbital nerve, supratrochlear nerve

CHRONIC NON-CANCER ABDOMINAL WALL PAIN AMELIORATION VIA PHENOL NEUROLYSIS BY TRANVERSUS ABDOMINIS PLANE APPROACH: A CASE REPORT

Abdominal pain is common and has multiple etiologies. We present a case of chronic abdominal wall pain that was treated with phenol neurolysis via a tranversus abdominis plane (TAP). To date, only 4 case reports utilizing TAP neurolysis have been reported and all were performed in the context of malignancy-related pain. The TAP block has become an integral component of the regional anesthesiologist’s perioperative anesthesia and analgesia arsenal. In summary, chemical denervation of the anterior abdominal wall is feasible and efficacious in palliating chronic non-cancer pain via a TAP block technique. Key words: TAP, transversus abdominal plane, phenol, abdominal wall pain, neurolytic, noncancer pain

A new experimental model of intrinsic denervation in ileum from wistar rats through intramural microinjections of benzalkonium chloride

ABSTRACT: Extensive literature is available about the intrinsic denervation of segments of the digestive tube through the application of CB in the serosa of the viscera. However, this technique has some disadvantages like causing peritonitis, flanges and high mortality, limiting its use in humans. The aim of the present study was to evaluate the feasibility of benzalkonium chloride (CB) to induce intrinsic chemical denervation, through applications of CB in the intramural ileum of wistar rats, as well as deepen the knowledge about the evolution of neuronal injury caused in the process. We used 40 rats, divided into two groups (control-GC and benzalkonium-GB) of 20 animals each, divided into four sub-groups according to the time of postoperative assessment of 24, 48 hours, 30 and 90 days. The animals were submitted to intramural microinjections of sterile saline solution 0.9% (GC) or benzalkonium chloride (GB) in ileal portion, and subsequent histopathological analysis and immunohistochemistry for evaluation of neuronal injury. A significant decrease (p<0.05) was found of the neuronal myenteric count over time in groups, GB3, GB4 and GB2. The specific positive immunolabeling for H2AX and Caspase-3 confirmed the results obtained in the histopathological evaluation, denoting the ignition of irreversible cell injury in 24 hours, evolving into neuronal apoptosis in 48 hours after application of the CB 0.3%. Under the conditions in which this work was conducted, it can be concluded that the application of CB 0.3% by means of microinjections intramural in the ileal wall is able to induce intrinsic chemical denervation of the diverticulum of wistar rats and that the main mechanism of neuronal death is induction of apoptosis.

Abstract 19072: Cardiac Autonomic Dysfunction in Mice Lacking Methyl CpG Binding Protein 2

Background: Rett Syndrome (RTT) is an X-linked dominant neurodevelopmental disorder primarily caused by mutations in Methyl-CpG-binding protein ( MECP2 ), a transcriptional regulator. Twenty-five percent of all deaths in RTT are sudden and unexpected, and autonomic nervous system (ANS) dysfunction is hypothesized to be the cause of sudden deaths in RTT. However, the role of MeCP2 in cardiac autonomic function has not been investigated in depth. Design/Methods: Male (2 months) and female (9 months) Mecp2 deficient and wildtype mice were implanted with ETA-F10 telemeters and 24h recordings were taken to calculate heart rate, heart rate variability, and incidence of arrhythmic events. Effects of pharmacological stimulants or inhibitors on heart rate were normalized to saline injection response. Results: Male Mecp2 deficient mice (NULL) have a decreased heart rate (WT = 634 ±3, NULL = 518 ±8, p<0.001), while female deficient mice (NULL/+) do not present with a decreased heart rate. Interestingly, NULL and NULL/+ mice both have a high incidence of sinus pauses and AV block (WT 1/5, NULL 6/6, NULL /+ 4/4, p<0.05). Additionally, both NULL and NULL/+ mice have increased bradycardia events defined as a heart rate below 200 bpm, (WT = 17 ±6, NULL = 307 ±94, NULL/+ = 198 ±67, p<0.05) and an increased heart rate variability. The normalized heart rate response to atropine, a parasympathetic blocker, of NULL mice was above wildtype levels (p<0.05) Chemical denervation by combined antagonism of parasympathetic (atropine) and sympathetic (propranolol) resulted in NULL mice having an increased normalized heart rate response compared to wildtype (p<0.05). Finally, the incidence of AVB/sinus pauses counts per 30 minutes post-acute treatment with atropine and chemical denervation (NULL saline 49 ±10, NULL atropine 8 ±5, NULL atropine/propranolol 0.5 ±0.5 p<0.05) decreased the severity of the cardiac phenotype in NULL mice. Conclusions: In summary, Mecp2 is required for a normal heart rhythm. Loss of Mecp2 causes bradycardia, sinus pauses, AV block, and increased heart rate variability that may be attributed by aberrant innervation. Acute atropine and chemical denervation was therapeutic and ameliorated the cardiac phenotype observed in Mecp2 deficient mice.