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Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones.
J Endocrinol. 2017 Jul; 234(1):R1-R21.JE

Abstract

Fatty liver can be diet, endocrine, drug, virus or genetically induced. Independent of cause, hepatic lipid accumulation promotes systemic metabolic dysfunction. By acting as peroxisome proliferator-activated receptor (PPAR) ligands, hepatic non-esterified fatty acids upregulate expression of gluconeogenic, beta-oxidative, lipogenic and ketogenic genes, promoting hyperglycemia, hyperlipidemia and ketosis. The typical hormonal environment in fatty liver disease consists of hyperinsulinemia, hyperglucagonemia, hypercortisolemia, growth hormone deficiency and elevated sympathetic tone. These endocrine and metabolic changes further encourage hepatic steatosis by regulating adipose tissue lipolysis, liver lipid uptake, de novo lipogenesis (DNL), beta-oxidation, ketogenesis and lipid export. Hepatic lipid accumulation may be induced by 4 separate mechanisms: (1) increased hepatic uptake of circulating fatty acids, (2) increased hepatic de novo fatty acid synthesis, (3) decreased hepatic beta-oxidation and (4) decreased hepatic lipid export. This review will discuss the hormonal regulation of each mechanism comparing multiple physiological models of hepatic lipid accumulation. Nonalcoholic fatty liver disease (NAFLD) is typified by increased hepatic lipid uptake, synthesis, oxidation and export. Chronic hepatic lipid signaling through PPARgamma results in gene expression changes that allow concurrent activity of DNL and beta-oxidation. The importance of hepatic steatosis in driving systemic metabolic dysfunction is highlighted by the common endocrine and metabolic disturbances across many conditions that result in fatty liver. Understanding the mechanisms underlying the metabolic dysfunction that develops as a consequence of hepatic lipid accumulation is critical to identifying points of intervention in this increasingly prevalent disease state.

Authors+Show Affiliations

School of Animal and Comparative Biomedical SciencesUniversity of Arizona, Tucson, Arizona, USA.School of Animal and Comparative Biomedical SciencesUniversity of Arizona, Tucson, Arizona, USA bjrenquist@email.arizona.edu.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

28428362

Citation

Geisler, Caroline E., and Benjamin J. Renquist. "Hepatic Lipid Accumulation: Cause and Consequence of Dysregulated Glucoregulatory Hormones." The Journal of Endocrinology, vol. 234, no. 1, 2017, pp. R1-R21.
Geisler CE, Renquist BJ. Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones. J Endocrinol. 2017;234(1):R1-R21.
Geisler, C. E., & Renquist, B. J. (2017). Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones. The Journal of Endocrinology, 234(1), R1-R21. https://doi.org/10.1530/JOE-16-0513
Geisler CE, Renquist BJ. Hepatic Lipid Accumulation: Cause and Consequence of Dysregulated Glucoregulatory Hormones. J Endocrinol. 2017;234(1):R1-R21. PubMed PMID: 28428362.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones. AU - Geisler,Caroline E, AU - Renquist,Benjamin J, Y1 - 2017/04/20/ PY - 2017/04/10/received PY - 2017/04/20/accepted PY - 2017/4/22/pubmed PY - 2017/7/25/medline PY - 2017/4/22/entrez KW - insulin resistance KW - nonalcoholic fatty liver disease KW - obesity KW - peroxisome proliferator-activated receptor SP - R1 EP - R21 JF - The Journal of endocrinology JO - J. Endocrinol. VL - 234 IS - 1 N2 - Fatty liver can be diet, endocrine, drug, virus or genetically induced. Independent of cause, hepatic lipid accumulation promotes systemic metabolic dysfunction. By acting as peroxisome proliferator-activated receptor (PPAR) ligands, hepatic non-esterified fatty acids upregulate expression of gluconeogenic, beta-oxidative, lipogenic and ketogenic genes, promoting hyperglycemia, hyperlipidemia and ketosis. The typical hormonal environment in fatty liver disease consists of hyperinsulinemia, hyperglucagonemia, hypercortisolemia, growth hormone deficiency and elevated sympathetic tone. These endocrine and metabolic changes further encourage hepatic steatosis by regulating adipose tissue lipolysis, liver lipid uptake, de novo lipogenesis (DNL), beta-oxidation, ketogenesis and lipid export. Hepatic lipid accumulation may be induced by 4 separate mechanisms: (1) increased hepatic uptake of circulating fatty acids, (2) increased hepatic de novo fatty acid synthesis, (3) decreased hepatic beta-oxidation and (4) decreased hepatic lipid export. This review will discuss the hormonal regulation of each mechanism comparing multiple physiological models of hepatic lipid accumulation. Nonalcoholic fatty liver disease (NAFLD) is typified by increased hepatic lipid uptake, synthesis, oxidation and export. Chronic hepatic lipid signaling through PPARgamma results in gene expression changes that allow concurrent activity of DNL and beta-oxidation. The importance of hepatic steatosis in driving systemic metabolic dysfunction is highlighted by the common endocrine and metabolic disturbances across many conditions that result in fatty liver. Understanding the mechanisms underlying the metabolic dysfunction that develops as a consequence of hepatic lipid accumulation is critical to identifying points of intervention in this increasingly prevalent disease state. SN - 1479-6805 UR - https://www.unboundmedicine.com/medline/citation/28428362/Hepatic_lipid_accumulation:_cause_and_consequence_of_dysregulated_glucoregulatory_hormones_ L2 - https://joe.bioscientifica.com/doi/10.1530/JOE-16-0513 DB - PRIME DP - Unbound Medicine ER -