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Article ; Online: Measurement of Basal and Forskolin-stimulated Lipolysis in Inguinal Adipose Fat Pads.

Baskaran, Padmamalini / Thyagarajan, Baskaran

Journal of visualized experiments : JoVE

2017 , Issue 125

Abstract: Lipolysis is a process by which the lipid stored as triglycerides in adipose tissues are hydrolyzed into glycerol and fatty acids. This article describes the method for the measurement of basal and forskolin (FSK)-stimulated lipolysis in the inguinal fat ...

Abstract	Lipolysis is a process by which the lipid stored as triglycerides in adipose tissues are hydrolyzed into glycerol and fatty acids. This article describes the method for the measurement of basal and forskolin (FSK)-stimulated lipolysis in the inguinal fat pads isolated from wild type mice fed either normal chow diet (NCD), high fat diet (HFD) or a high fat diet containing 0.01% of capsaicin (CAP; transient receptor potential vanilloid subfamily 1 (TRPV1) agonist) for 32 weeks. The method described here for performing ex vivo lipolysis is adopted from Schweiger et al.
MeSH term(s)	Adipose Tissue/drug effects ; Adipose Tissue/metabolism ; Animals ; Colforsin/pharmacology ; Diet, High-Fat ; Glycerol/analysis ; Glycerol/metabolism ; Lipolysis/drug effects ; Male ; Mice ; Spectrophotometry/methods
Chemical Substances	Colforsin (1F7A44V6OU) ; Glycerol (PDC6A3C0OX)
Language	English
Publishing date	2017-07-21
Publishing country	United States
Document type	Journal Article ; Video-Audio Media ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1940-087X
ISSN (online)	1940-087X
DOI	10.3791/55625
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Article ; Online: Mice lacking endogenous TRPV1 express reduced levels of thermogenic proteins and are susceptible to diet-induced obesity and metabolic dysfunction.

Baskaran, Padmamalini / Nazminia, Kara / Frantz, Justine / O'Neal, Jessica / Thyagarajan, Baskaran

FEBS letters

2021 Volume 595, Issue 13, Page(s) 1768–1781

Abstract: Transient receptor potential vanilloid subfamily 1 (TRPV1) is a non-selective cation channel protein expressed in neuronal and non-neuronal cells. Although TRPV1 is implicated in thermogenesis and diet-induced obesity (DIO), its precise role remains ... ...

Abstract	Transient receptor potential vanilloid subfamily 1 (TRPV1) is a non-selective cation channel protein expressed in neuronal and non-neuronal cells. Although TRPV1 is implicated in thermogenesis and diet-induced obesity (DIO), its precise role remains controversial. TRPV1
MeSH term(s)	Adipose Tissue, Brown/drug effects ; Adipose Tissue, Brown/metabolism ; Adipose Tissue, White/drug effects ; Adipose Tissue, White/metabolism ; Animals ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; Gene Expression Regulation/drug effects ; Gene Knockdown Techniques ; Gene Regulatory Networks/drug effects ; Male ; Metabolic Syndrome/chemically induced ; Metabolic Syndrome/genetics ; Metabolic Syndrome/metabolism ; Mice ; Obesity/chemically induced ; Obesity/genetics ; Obesity/metabolism ; TRPV Cation Channels/genetics ; Thermogenesis
Chemical Substances	TRPV Cation Channels ; TRPV1 protein, mouse
Language	English
Publishing date	2021-05-30
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	212746-5
ISSN	1873-3468 ; 0014-5793
ISSN (online)	1873-3468
ISSN	0014-5793
DOI	10.1002/1873-3468.14105
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Article ; Online: Pain pathways and potential new targets for pain relief.

Wang, Menglan / Thyagarajan, Baskaran

Biotechnology and applied biochemistry

2020 Volume 69, Issue 1, Page(s) 110–123

Abstract: Pain is an unpleasant sensory and emotional experience that affects a sizable percentage of people on a daily basis. Sensory neurons known as nociceptors built specifically to detect damaging stimuli can be found throughout the body. They transmit ... ...

Abstract	Pain is an unpleasant sensory and emotional experience that affects a sizable percentage of people on a daily basis. Sensory neurons known as nociceptors built specifically to detect damaging stimuli can be found throughout the body. They transmit information about noxious stimuli from mechanical, thermal, and chemical sources to the central nervous system and higher brain centers via electrical signals. Nociceptors express various channels and receptors such as voltage-gated sodium and calcium channels, transient receptor potential channels, and opioid receptors that allow them to respond in a highly specific manner to noxious stimuli. Attenuating the pain response can be achieved by inhibiting or altering the expression of these pain targets. Achieving a deeper understanding of how these receptors can be affected at the molecular level can lead to the development of novel pain therapies. This review will discuss the mechanisms of pain, introduce the various receptors that are responsible for detecting pain, and future directions in pharmacological therapies.
MeSH term(s)	Humans ; Nociceptors ; Pain/drug therapy ; Sodium
Chemical Substances	Sodium (9NEZ333N27)
Language	English
Publishing date	2020-12-27
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	883433-7
ISSN	1470-8744 ; 0885-4513
ISSN (online)	1470-8744
ISSN	0885-4513
DOI	10.1002/bab.2086
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Article ; Online: Preparation and Evaluation of PLGA-Coated Capsaicin Magnetic Nanoparticles.

Baskaran, Mrudhula / Baskaran, Padmamalini / Arulsamy, Navamoney / Thyagarajan, Baskaran

Pharmaceutical research

2017 Volume 34, Issue 6, Page(s) 1255–1263

Abstract: Purpose: Drugs used in the treatment of diseases can cause several unwanted systemic side effects. A site-specific drug delivery system can eliminate such consequences by delivering drugs to certain target areas of the body where therapeutic effects are ...

Abstract	Purpose: Drugs used in the treatment of diseases can cause several unwanted systemic side effects. A site-specific drug delivery system can eliminate such consequences by delivering drugs to certain target areas of the body where therapeutic effects are required. Here we present the preparation and evaluation of magnetic nanoparticles of capsaicin, the active ingredient in chili peppers, coated with poly-L-lactide co-glycolide (PLGA), a FDA-approved biodegradable bioavailable polymer. Methods: PCMN were prepared by solvent-evaporation/coprecipitation technique and their physicochemical and pharmacological characteristics evaluated in vitro. Further, effective pain/inflammation therapeutics of PCMN in a mouse model of inflammation was also studied. We also prepared and evaluated the subcellular localization of PLGA coated fluorescence magnetic nanoparticle (PFMN) in vitro in HEK293 cells. Results: Transmission electron microscopic images of PCMN showed that the size of the nanoparticles were of the order of 10-20 nm. PCMN showed approximately 9.29% drug loading and 89.15% encapsulation efficiencies. In vitro dissolution studies showed an increased solubility of capsaicin due to the nano-size of the PCMN, while PLGA coating allowed sustained release of capsaicin in vitro. The PCMN also reduced paw edema after injection in mice, and confocal microscopy revealed the successful intracellular localization of PLGA-coated fluorescein magnetic nanoparticles in HEK293 cells. Conclusion: The PCMN provided a sustained release of capsaicin in vitro and inhibited carrageenan-induced inflammatory pain in mouse model in vivo. These data suggest that PLGA coating of capsaicin magnetic nanoparticles have the potential to be amenable for a sustained release of capsaicin to relieve pain.
MeSH term(s)	Animals ; Capsaicin/chemistry ; Capsaicin/pharmacology ; Cell Survival/drug effects ; Delayed-Action Preparations ; Drug Carriers ; Drug Liberation ; Fluorescein/chemistry ; Fluorescent Dyes/chemistry ; HEK293 Cells ; Humans ; Inflammation/drug therapy ; Lactic Acid/chemistry ; Magnetite Nanoparticles/chemistry ; Male ; Mice, Inbred C57BL ; Pain/drug therapy ; Particle Size ; Polyglycolic Acid/chemistry ; Solubility ; Surface Properties
Chemical Substances	Delayed-Action Preparations ; Drug Carriers ; Fluorescent Dyes ; Magnetite Nanoparticles ; polylactic acid-polyglycolic acid copolymer ; Polyglycolic Acid (26009-03-0) ; Lactic Acid (33X04XA5AT) ; Capsaicin (S07O44R1ZM) ; Fluorescein (TPY09G7XIR)
Language	English
Publishing date	2017-03-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	843063-9
ISSN	1573-904X ; 0724-8741 ; 0739-0742
ISSN (online)	1573-904X
ISSN	0724-8741 ; 0739-0742
DOI	10.1007/s11095-017-2142-2
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Article ; Online: Evaluation of a polymer-coated nanoparticle cream formulation of resiniferatoxin for the treatment of painful diabetic peripheral neuropathy.

Baskaran, Padmamalini / Mohandass, Adithya / Gustafson, Noah / Bennis, Jane / Louis, Somaja / Alexander, Brenda / Nemenov, Mikhail I / Thyagarajan, Baskaran / Premkumar, Louis S

Pain

2022 Volume 164, Issue 4, Page(s) 782–790

Abstract: Abstract: Painful diabetic peripheral neuropathy (PDPN) is one of the major complications of diabetes. Currently, centrally acting drugs and topical analgesics are used for treating PDPN. These drugs have adverse effects; some are ineffective, and ... ...

Abstract	Abstract: Painful diabetic peripheral neuropathy (PDPN) is one of the major complications of diabetes. Currently, centrally acting drugs and topical analgesics are used for treating PDPN. These drugs have adverse effects; some are ineffective, and treatment with opioids is associated with use dependence and addiction. Recent research indicates that transient receptor potential vanilloid 1 (TRPV1) expressed in the peripheral sensory nerve terminals is an emerging target to treat pain associated with PDPN. Block of TRPV1 ion channel with specific antagonists, although effective as an analgesic, induced hyperthermia in clinical trials. However, TRPV1 agonists are useful to treat pain by virtue of their ability to cause Ca 2+ influx and subsequently leading to nerve terminal desensitization. Here, we report the effectiveness of an ultrapotent TRPV1 agonist, resiniferatoxin (RTX) nanoparticle, in a topical formulation (RTX-cream; RESINIZIN) that alleviates pain associated with DPN in animal models of diabetes. Resiniferatoxin causes nerve terminal depolarization block in the short term, which prevents pain during application and leading to nerve terminal desensitization/depletion in the long term resulting in long-lasting pain relief. Application of RTX cream to the hind limbs suppresses thermal hyperalgesia in streptozotocin-induced diabetic rats and mini pigs without any adverse effects as compared with capsaicin at therapeutic doses, which induces intense pain during application. Resiniferatoxin cream also decreases the expression of TRPV1 in the peripheral nerve endings and suppresses TRPV1-mediated calcitonin gene-related peptide release in the skin samples of diabetic rats and mini pigs. Our preclinical data confirm that RTX topical formulation is an effective treatment option for PDPN.
MeSH term(s)	Swine ; Rats ; Animals ; Diabetic Neuropathies/drug therapy ; Diabetes Mellitus, Experimental/complications ; Diabetes Mellitus, Experimental/drug therapy ; Swine, Miniature/metabolism ; Pain ; Diterpenes/therapeutic use ; Analgesics/therapeutic use ; Capsaicin/pharmacology ; TRPV Cation Channels/metabolism
Chemical Substances	resiniferatoxin (A5O6P1UL4I) ; Diterpenes ; Analgesics ; Capsaicin (S07O44R1ZM) ; TRPV Cation Channels
Language	English
Publishing date	2022-08-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	193153-2
ISSN	1872-6623 ; 0304-3959
ISSN (online)	1872-6623
ISSN	0304-3959
DOI	10.1097/j.pain.0000000000002765
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Article ; Online: Troglitazone activates TRPV1 and causes deacetylation of PPARγ in 3T3-L1 cells.

Krishnan, Vivek / Baskaran, Padmamalini / Thyagarajan, Baskaran

Biochimica et biophysica acta. Molecular basis of disease

2018 Volume 1865, Issue 2, Page(s) 445–453

Abstract: Published research suggests that activation of transient receptor potential vanilloid subfamily 1 (TRPV1) enhances the expression and deacetylation of peroxisome proliferator-activated receptor gamma (PPARγ) to cause browning of white adipose tissue. ... ...

Abstract	Published research suggests that activation of transient receptor potential vanilloid subfamily 1 (TRPV1) enhances the expression and deacetylation of peroxisome proliferator-activated receptor gamma (PPARγ) to cause browning of white adipose tissue. Here, we show that TRPV1 activation by capsaicin significantly prevents high fat diet-induced obesity in mice. This is associated with an increase in the expression and deacetylation of PPARγ in the epididymal fat of these mice. Consistent with the TRPV1 activation in vivo, overexpression of TRPV1 enhanced the PPARγ and other thermogenic genes in cultured 3T3-L1 preadipocytes. To determine the interaction between TRPV1 and PPARγ signaling, we analyzed the effect of Troglitazone (Trog; a thiazolidinedione derivative and an agonist of PAARγ) treatment on cultured 3T3-L1 cells. Trog enhanced the expression of TRPV1, PPARγ and thermogenic proteins in undifferentiated 3T3-L1 cells but not in differentiated cells. Acute application of Trog stimulated a robust Ca
MeSH term(s)	3T3-L1 Cells ; Acetylation/drug effects ; Adipogenesis/drug effects ; Adipogenesis/genetics ; Adipose Tissue/drug effects ; Adipose Tissue/metabolism ; Animals ; Bone Morphogenetic Proteins/metabolism ; CCAAT-Enhancer-Binding Proteins/metabolism ; Capsaicin/analogs & derivatives ; Capsaicin/pharmacology ; Diet, High-Fat ; Epididymis/drug effects ; Epididymis/metabolism ; Feeding Behavior ; Ion Channel Gating/drug effects ; Lipid Metabolism ; Male ; Mice ; PPAR alpha/metabolism ; PPAR gamma/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Sirtuin 1/genetics ; Sirtuin 1/metabolism ; TRPV Cation Channels/metabolism ; Thermogenesis/genetics ; Troglitazone/pharmacology ; Uncoupling Protein 1/metabolism ; Weight Loss/drug effects
Chemical Substances	Bmp8b protein, mouse ; Bone Morphogenetic Proteins ; CCAAT-Enhancer-Binding Proteins ; CEBPA protein, mouse ; PPAR alpha ; PPAR gamma ; RNA, Messenger ; TRPV Cation Channels ; TRPV1 receptor ; Uncoupling Protein 1 ; Sirtuin 1 (EC 3.5.1.-) ; Troglitazone (I66ZZ0ZN0E) ; capsazepine (LFW48MY844) ; Capsaicin (S07O44R1ZM)
Language	English
Publishing date	2018-11-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbadis.2018.11.004
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Article: Mice lacking endogenous TRPV1 express reduced levels of thermogenic proteins and are susceptible to diet‐induced obesity and metabolic dysfunction

Baskaran, Padmamalini / Nazminia, Kara / Frantz, Justine / O’Neal, Jessica / Thyagarajan, Baskaran

FEBS letters. 2021 July, v. 595, no. 13

2021

Abstract: Transient receptor potential vanilloid subfamily 1 (TRPV1) is a non‐selective cation channel protein expressed in neuronal and non‐neuronal cells. Although TRPV1 is implicated in thermogenesis and diet‐induced obesity (DIO), its precise role remains ... ...

Abstract	Transient receptor potential vanilloid subfamily 1 (TRPV1) is a non‐selective cation channel protein expressed in neuronal and non‐neuronal cells. Although TRPV1 is implicated in thermogenesis and diet‐induced obesity (DIO), its precise role remains controversial. TRPV1⁻/⁻ mice are protected from DIO, while TRPV1 activation enhances thermogenesis to prevent obesity. To reconcile this, we fed wild‐type and TRPV1⁻/⁻ mice for 32 weeks with normal chow or a high‐fat diet and analyzed the weight gain, metabolic activities, and thermogenic protein expression in white and brown fats. TRPV1⁻/⁻ mice became obese, exhibited reduced locomotor activity, reduced energy expenditure, enhanced hepatic steatosis, and decreased thermogenic protein expression in adipose tissues. Our data reveal that lack of TRPV1 does not prevent obesity, but rather enhances metabolic dysfunction.
Keywords	energy expenditure ; fatty liver ; heat production ; high fat diet ; locomotion ; neurons ; obesity ; protein synthesis ; transient receptor potential vanilloid channels ; weight gain
Language	English
Dates of publication	2021-07
Size	p. 1768-1781.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	212746-5
ISSN	1873-3468 ; 0014-5793
ISSN (online)	1873-3468
ISSN	0014-5793
DOI	10.1002/1873-3468.14105
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Article ; Online: Consumer's Opinion on a Pharmacist's Role in Nutritional Counseling.

Meier, Megan / Singh, Reshmi L / Thyagarajan, Baskaran

Innovations in pharmacy

2021 Volume 12, Issue 2

Abstract: Background: Nutrition has become an increasing health concern. From fad diets to exercise programs, the consumer seems to be consulting multiple resources that all provide a different answer in the process of obtaining optimal health. Easily accessible ... ...

Abstract	Background: Nutrition has become an increasing health concern. From fad diets to exercise programs, the consumer seems to be consulting multiple resources that all provide a different answer in the process of obtaining optimal health. Easily accessible pharmacists may be the sources to answer crucial nutritional issues facing society today. Methods: Using the results of a previous study about food perceptions among lean and non-lean populations, interview questions were created to determine the populations' nutrition and pharmacist's role knowledge. Nutrition knowledge among lean vs. non-lean consumers was assessed by determining experience with pharmacist nutritional counseling, how experience perceptions differed, and how these perceptions can shape a pharmacist's role. Audio recorded interviews were conducted in a rural setting. Seventy-two English speaking, ambulatory, lean (BMI ≤ 24) and non-lean (BMI ≥ 25) residents between the ages 25-71 years participated in the study in a small western United States town. Results: 26.3% of consumers obtained nutrition information from the internet; however, the internet and healthcare providers were considered the most trustworthy. When asked about the pharmacist's role in nutrition counseling, 32.7% believed that pharmacists were not a reliable source based on education background. Another 10.2% thought pharmacists were too busy for counseling. Discussion: This study indicates the consumers' knowledge on pharmacists' education, willingness to seek out nutrition knowledge, and a pharmacist's ability to provide nutrition counseling can differ between lean and non-lean consumers. Lean consumers tend to have more interaction with a pharmacist whereas non-lean consumers do not. Conclusion: As a profession, pharmacists should educate consumers on reliable nutrition resources, a pharmacist's education, and how they use their role to provide consumers with nutrition knowledge.
Language	English
Publishing date	2021-04-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2689516-X
ISSN	2155-0417 ; 2155-0417
ISSN (online)	2155-0417
ISSN	2155-0417
DOI	10.24926/iip.v12i2.3634
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Article ; Online: Kainic Acid Activates TRPV1 via a Phospholipase C/PIP2-Dependent Mechanism in Vitro.

Mohandass, Adithya / Surenkhuu, Bayasgalan / Covington, Kyle / Baskaran, Padmamalini / Lehmann, Teresa / Thyagarajan, Baskaran

ACS chemical neuroscience

2020 Volume 11, Issue 19, Page(s) 2999–3007

Abstract: Kainic acid (KA) is an excitotoxic glutamate analogue produced by a marine seaweed. It elicits neuronal excitotoxicity leading to epilepsy in rodents. Activation of transient receptor potential vanilloid subfamily 1 (TRPV1), a nonselective cation channel ...

Abstract	Kainic acid (KA) is an excitotoxic glutamate analogue produced by a marine seaweed. It elicits neuronal excitotoxicity leading to epilepsy in rodents. Activation of transient receptor potential vanilloid subfamily 1 (TRPV1), a nonselective cation channel protein, by capsaicin, prevents KA-induced seizures in a mouse model of temporal lobe epilepsy. However, the precise mechanism behind this protective effect of capsaicin remains unclear. In order to analyze the direct effect of KA on TRPV1, we evaluated the ability of KA to activate TRPV1 and analyzed its binding to TRPV1 using a molecular modeling approach. In vitro, KA activates a Ca
MeSH term(s)	Capsaicin/pharmacology ; HEK293 Cells ; Humans ; Kainic Acid/toxicity ; Phosphatidylinositols ; TRPV Cation Channels ; Type C Phospholipases/metabolism
Chemical Substances	Phosphatidylinositols ; TRPV Cation Channels ; TRPV1 protein, human ; Type C Phospholipases (EC 3.1.4.-) ; Capsaicin (S07O44R1ZM) ; Kainic Acid (SIV03811UC)
Language	English
Publishing date	2020-09-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/acschemneuro.0c00297
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Article: Measurement of basal and forskolin-stimulated lipolysis in inguinal adipose fat pads

Baskaran, Padmamalini / Thyagarajan, Baskaran

Journal of visualized experiments. 2017 July 21, , no. 125

2017

Abstract	Lipolysis is a process by which the lipid stored as triglycerides in adipose tissues are hydrolyzed into glycerol and fatty acids. This article describes the method for the measurement of basal and forskolin (FSK)-stimulated lipolysis in the inguinal fat pads isolated from wild type mice fed either normal chow diet (NCD), high fat diet (HFD) or a high fat diet containing 0.01% of capsaicin (CAP; transient receptor potential vanilloid subfamily 1 (TRPV1) agonist) for 32 weeks. The method described here for performing ex vivo lipolysis is adopted from Schweiger et al.1 We present a detailed protocol for measuring glycerol levels by UV-Visible (UV/VIS) spectrophotometry. The method described here can be used to successfully isolate inguinal fat pads for lipolysis measurements to obtain consistent results. The protocol described for inguinal fat pads can readily be extended to measure lipolysis in other tissues.
Keywords	adipose tissue ; agonists ; capsaicin ; fatty acids ; forskolin ; glycerol ; high fat diet ; lipolysis ; mice ; transient receptor potential vanilloid channels ; triacylglycerols ; ultraviolet-visible spectroscopy
Language	English
Dates of publication	2017-0721
Size	p. e55625.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/55625
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