Khandelwal N

References (4)

Title : A multi-omics analysis reveals that the lysine deacetylase ABHD14B influences glucose metabolism in mammals - Rajendran_2022_J.Biol.Chem_298_102128
Author(s) : Rajendran A , Soory A , Khandelwal N , Ratnaparkhi G , Kamat SS
Ref : Journal of Biological Chemistry , 298 :102128 , 2022
Abstract : The sirtuins and histone deacetylases are the best characterized members of the lysine deacetylase (KDAC) enzyme family. Recently, we annotated the "orphan" enzyme ABHD14B (alpha/beta-hydrolase domain containing protein # 14B) as a novel KDAC, showed this enzyme's ability to transfer an acetyl-group from protein lysine residue(s) to coenzyme-A (CoA) to yield acetyl-CoA, expanding the repertoire of this enzyme family. However, the role of ABHD14B in metabolic processes is not fully elucidated. Here, we investigated the role of this enzyme using mammalian cell knockdowns in a combined transcriptomics, and metabolomics analysis. We found from these complementary experiments in vivo, that the loss of ABHD14B results in significantly altered glucose metabolism, specifically the decreased flux of glucose through glycolysis and the citric acid cycle. Further, we show that depleting hepatic ABHD14B in mice, also results in defective systemic glucose metabolism, particularly during fasting. Taken together, our findings illuminate the important metabolic functions that the KDAC ABHD14B plays in mammalian physiology, and poses new questions regarding the role of this hitherto cryptic metabolism-regulating enzyme.
ESTHER : Rajendran_2022_J.Biol.Chem_298_102128
PubMedSearch : Rajendran_2022_J.Biol.Chem_298_102128
PubMedID: 35700823
Gene_locus related to this paper: human-CIB

Title : Fatty acid chain length drives lysophosphatidylserine-dependent immunological outputs - Khandelwal_2021_Cell.Chem.Biol__
Author(s) : Khandelwal N , Shaikh M , Mhetre A , Singh S , Sajeevan T , Joshi A , Balaji KN , Chakrapani H , Kamat SS
Ref : Cell Chemical Biology , : , 2021
Abstract : In humans, lysophosphatidylserines (lyso-PSs) are potent lipid regulators of important immunological processes. Given their structural diversity and commercial paucity, here we report the synthesis of methyl esters of lyso-PS (Me-lyso-PSs) containing medium- to very-long-chain (VLC) lipid tails. We show that Me-lyso-PSs are excellent substrates for the lyso-PS lipase ABHD12, and that these synthetic lipids are acted upon by cellular carboxylesterases to produce lyso-PSs. Next, in macrophages we demonstrate that VLC lyso-PSs orchestrate pro-inflammatory responses and in turn neuroinflammation via a Toll-like receptor 2 (TLR2)-dependent pathway. We also show that long-chain (LC) lyso-PSs robustly induce intracellular cyclic AMP production, cytosolic calcium influx, and phosphorylation of the nodal extracellular signal-regulated kinase to regulate macrophage activation via a TLR2-independent pathway. Finally, we report that LC lyso-PSs potently elicit histamine release during the mast cell degranulation process, and that ABHD12 is the major lyso-PS lipase in these immune cells.
ESTHER : Khandelwal_2021_Cell.Chem.Biol__
PubMedSearch : Khandelwal_2021_Cell.Chem.Biol__
PubMedID: 33571455
Gene_locus related to this paper: human-ABHD12

Title : Efficacy of Bacopa Monnieri (Brahmi) and Donepezil in Alzheimer's Disease and Mild Cognitive Impairment: A Randomized Double-Blind Parallel Phase 2b Study - Prabhakar_2020_Ann.Indian.Acad.Neurol_23_767
Author(s) : Prabhakar S , Vishnu VY , Modi M , Mohanty M , Sharma A , Medhi B , Mittal BR , Khandelwal N , Goyal MK , Lal V , Singla R , Kansal A , Avasthi A
Ref : Ann Indian Acad Neurol , 23 :767 , 2020
Abstract : OBJECTIVES: Alzheimer's disease (AD) is the most common cause of dementia worldwide in the older population. There is no disease-modifying therapy available for AD. The current standard of care drug therapy for AD is cholinesterase inhibitors, including donepezil. Bacopa monnieri or brahmi is used in traditional Indian medicine for memory loss. We conducted a phase 2b randomized controlled trial (RCT) to find out the efficacy of brahmi and donepezil in AD and mild cognitive impairment (MCI). PATIENTS AND METHODS: The study was planned as a 52 week, randomized, double-blind, parallel-group, phase-2 single-center clinical trial comparing the efficacy and safety of Bacopa monnieri (brahmi) 300 mg OD and donepezil 10 mg OD for 12 months in 48 patients with AD and MCI-AD including cognitive and quality of life outcomes. The primary outcome was differences in the change from baseline of the neuropsychological tests [Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog) and postgraduate institute (PGI) memory scale] at 12 months between the intervention group (brahmi) and active comparison group (donepezil). RESULTS: The study was terminated after 3 years and 9 months, after recruiting 34 patients, because of slow recruitment and a high dropout rate. Intention to treat analysis after adjusting for baseline confounders showed no difference in the rate of change in ADAS-Cog score from baseline at any time point, including the last follow-up. There was no difference in the rate of change in PGI Memory scale (PGIMS) at 3, 6, and 9 months. In the last follow-up, there was a significant difference in the change in total PGIMS score between brahmi and donepezil, while there was no difference in individual scores of the PGI memory scale. CONCLUSION: This phase-2 RCT on the efficacy of brahmi vs. donepezil showed no significant difference between them after 1 year of treatment. Larger phase-3 trials, preferably multicentric, are required to find the superiority of brahmi over donepezil.
ESTHER : Prabhakar_2020_Ann.Indian.Acad.Neurol_23_767
PubMedSearch : Prabhakar_2020_Ann.Indian.Acad.Neurol_23_767
PubMedID: 33688125

Title : The Lysophosphatidylserines-An Emerging Class of Signalling Lysophospholipids - Shanbhag_2020_J.Membr.Biol_253_381
Author(s) : Shanbhag K , Mhetre A , Khandelwal N , Kamat SS
Ref : J Membr Biol , 253 :381 , 2020
Abstract : Lysophospholipids are potent hormone-like signalling biological lipids that regulate many important biological processes in mammals (including humans). Lysophosphatidic acid and sphingosine-1-phosphate represent the best studied examples for this lipid class, and their metabolic enzymes and/or cognate receptors are currently under clinical investigation for treatment of various neurological and autoimmune diseases in humans. Over the past two decades, the lysophsophatidylserines (lyso-PSs) have emerged as yet another biologically important lysophospholipid, and deregulation in its metabolism has been linked to various human pathophysiological conditions. Despite its recent emergence, an exhaustive review summarizing recent advances on lyso-PSs and the biological pathways that this bioactive lysophospholipid regulates has been lacking. To address this, here, we summarize studies that led to the discovery of lyso-PS as a potent signalling biomolecule, and discuss the structure, its detection in biological systems, and the biodistribution of this lysophospholipid in various mammalian systems. Further, we describe in detail the enzymatic pathways that are involved in the biosynthesis and degradation of this lipid and the putative lyso-PS receptors reported in the literature. Finally, we discuss the various biological pathways directly regulated by lyso-PSs in mammals and prospect new questions for this still emerging biomedically important signalling lysophospholipid.
ESTHER : Shanbhag_2020_J.Membr.Biol_253_381
PubMedSearch : Shanbhag_2020_J.Membr.Biol_253_381
PubMedID: 32767057