Jason Kronenfeld

All Publications

• A critical role of hepatic GABA in the metabolic dysfunction and hyperphagia of obesity CELL REPORTS Geisler, C. E., Ghimire, S., Bruggink, S. M., Miller, K. E., Weninger, S. N., Kronenfeld, J. M., Yoshino, J., Klein, S., Duca, F. A., Renquist, B. J. 2021; 35 (13): 109301

  Abstract

  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. Hepatic GABA-T inhibition and knockdown decreased basal hyperinsulinemia and hyperglycemia and improved glucose intolerance. GABA-T knockdown improved insulin sensitivity assessed by hyperinsulinemic-euglycemic clamps in obese mice. Hepatic GABA-T knockdown also decreased food intake and induced weight loss without altering energy expenditure in obese mice. Data from people with obesity support the notion that hepatic GABA production and transport are associated with serum insulin, homeostatic model assessment for insulin resistance (HOMA-IR), T2D, and BMI. These results support a key role for hepatocyte GABA production in the dysfunctional glucoregulation and feeding behavior associated with obesity.

  View details for DOI 10.1016/j.celrep.2021.109301

  View details for Web of Science ID 000668072600010

  View details for PubMedID 34192532

• Development of a GABA Transaminase Inhibitor That Does Not Penetrate the Blood-Brain Barrier Kronenfeld, J. M. The University of Arizona Honors College. Thesis Repository. 2021
• Feed intake-dependent and -independent effects of heat stress on lactation and mammary gland development JOURNAL OF DAIRY SCIENCE Xiao, Y., Kronenfeld, J. M., Renquist, B. J. 2020; 103 (12): 12003-12014

  Abstract

  With a growing population, a reliable food supply is increasingly important. Heat stress reduces livestock meat and milk production. Genetic selection of high-producing animals increases endogenous heat production, while climate change increases exogenous heat exposure. Both sources of heat exacerbate the risk of heat-induced depression of production. Rodents are valuable models to understand mechanisms conserved across species. Heat exposure suppresses feed intake across homeothermic species including rodents and production animal species. We assessed the response to early-mid lactation or late-gestation heat exposure on milk production and mammary gland development/function, respectively. Using pair-fed controls we experimentally isolated the feed intake-dependent and -independent effects of heat stress on mammary function and mass. Heat exposure (35°C, relative humidity 50%) decreased daily feed intake. When heat exposure occurred during lactation, hypophagia accounted for approximately 50% of the heat stress-induced hypogalactia. Heat exposure during middle to late gestation suppressed feed intake, which was fully responsible for the lowered mammary gland weight of dams at parturition. However, the impaired mammary gland function in heat-exposed dams measured by metabolic rate and lactogenesis could not be explained by depressed feed consumption. In conclusion, mice recapitulate the depressed milk production and mammary gland development observed in dairy species while providing insight regarding the role of feed intake. This opens the potential to apply genetic, experimental, and pharmacological models unique to mice to identify the mechanism by which heat is limiting animal production.

  View details for DOI 10.3168/jds.2020-18675

  View details for Web of Science ID 000603029300036

  View details for PubMedID 33041042

• Determining the Role of Obesity and Muscarinic Signaling in Asthma Bruggink, S., Kentch, K., Kronenfeld, J., Renquist, B. WILEY. 2020

  View details for DOI 10.1096/fasebj.2020.34.s1.05674

  View details for Web of Science ID 000546107901356

• It's Strong, It's Stable, It's Streptavidin Futch, L., Pham, T., Adamson, B., Reilly, B., Kronenfeld, J., Patterson, K., Inostroza, M., Fraijo, S., Montoya, J., Chavez, R., Hazzard, J. FEDERATION AMER SOC EXP BIOL. 2015

  View details for Web of Science ID 000361470500058