Evidence that the liver produces ketone bodies

"3.1. Endocrine Regulation

The general principle of hormonal regulation states that anabolic hormones inhibit, and catabolic hormones stimulate ketogenesis [5]. Insulin, which is the main anabolic hormone, is principally important: in the presence of insulin ketogenesis is strongly inhibited, even when catabolic hormones are also secreted. Insulin acts in two complementary manners: first, it blocks lipolysis in adipocytes; and next, it promotes glucose uptake and oxidation by tissues, which results in elevated succinyl-CoA and malonyl-CoA levels. These intermediates are strong inhibitors of fatty acid oxidation and ketone body formation in liver and other ketogenic tissues. When insulin levels are low, the catabolic hormones, namely glucagon (secreted by the pancreas during hypoglycemia), as well as cortisol, growth hormone, catecholamines, epinephrine, norepinephrine, and thyroid hormones come into prominence [6,7]. They all stimulate lipolysis and the release of free fatty acids, as well as fatty acid transport to the liver and skeletal muscles. Increased influx of fatty acids to the liver induces their β-oxidation and subsequent ketogenesis. Among catabolic hormones, epinephrine and norepinephrine, which drive “fight or flight” reactions to stress, are particularly strong activators of lipolysis, fatty acid oxidation and ketogenesis, and remain active regardless of insulin levels [8,9]."

Exercise

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407977/

Other circumstances

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187893/

Figure 1

The metabolism of ketone bodies: ketogenesis takes place in hepatocyte mitochondria, whereas ketolysis involves utilization of ketone bodies in the mitochondria of peripheral tissues. ACAT1—acetoacetyl-CoA thiolase, Ac-CoA—acetyl-CoA, AcAc-CoA—acetoacetyl-CoA, BDH—β-hydroxybutyrate dehydrogenase, bHB—β-hydroxybutyrate, CPT1—carnitine palmitoyltransferase 1, HMGCL—HMG-CoA lyase, HMGCS2—HMG-CoA synthetase, MCT1—monocarboxylate transporter 1, SCOT—succinyl-CoA:3-ketocid-CoA transferase, TCA—tricarboxylic acid cycle.

Figure 2

AMPK and mTOR complex 1 (mTORC1) respond to nutrient supply and cellular energy status. AMPK stimulates catabolism and ketogenesis through activation of PPARα and PGC-1α. mTORC1 blocks PPARα and induces anabolic processes, such as protein and lipid biosynthesis. The abbreviations are explained in the text.