Publications by authors named "Susma Ghimire"
Article Synopsis
- Hepatic lipid buildup in obesity leads to increased hyperinsulinemia and insulin resistance, affecting liver function.
- Hepatocyte depolarization reduces vagal nerve firing and heightens GABA release, contributing to hyperinsulinemia.
- Altering hepatic GABA release can improve insulin sensitivity and mitigate glucoregulatory issues in obesity, with implications for type 2 diabetes risk.
Hepatic lipid accumulation is a hallmark of type II diabetes (T2D) associated with hyperinsulinemia, insulin resistance, and hyperphagia. Hepatic synthesis of GABA, catalyzed by GABA-transaminase (GABA-T), is upregulated in obese mice. To assess the role of hepatic GABA production in obesity-induced metabolic and energy dysregulation, we treated mice with two pharmacologic GABA-T inhibitors and knocked down hepatic GABA-T expression using an antisense oligonucleotide.
View Article and Find Full Text PDFSignaling through GPR109a, the putative receptor for the endogenous ligand β-OH butyrate, inhibits adipose tissue lipolysis. Niacin, an anti-atherosclerotic drug that can induce insulin resistance, activates GPR109a at nM concentrations. GPR109a is not essential for niacin to improve serum lipid profiles.
View Article and Find Full Text PDFRole of ketone signaling in the hepatic response to fasting.
Am J Physiol Gastrointest Liver Physiol
May 2019
Article Synopsis
- Ketosis is a metabolic response that occurs during fasting, prolonged exercise, and conditions like nonalcoholic fatty liver disease (NAFLD), influenced by β-OH butyrate which affects cellular signaling.
- The study investigated how β-OH butyrate signaling impacts liver metabolism by comparing normal mice with HMGCS2 knockdown mice, which cannot produce β-OH butyrate.
- Results revealed that fasting increased specific protein expression related to fat metabolism in knockdown mice, and administering β-OH butyrate restored normal responses, suggesting its crucial role in regulating liver fat oxidation and glucose tolerance during fasting.
Background: The evolution of mortal somatic cells was a critical step in the evolution of complex body plans and the major radiations of multicellular life. In the volvocine green algae, somatic cells are hypothesized to mitigate an increasing cost of reproduction as colony size increases, primarily by providing motility to the colony during reproduction.
Questions: Does selection on colony size cause an evolutionary response in proportion of somatic cells? Does the effect of selection on colony size differ in environments that differ in the importance of motility?
Methods: We subjected an outcrossed population of the volvocine alga to selection on colony size in still and mixed environments.