Most interestingly, several candidate genes, including previously reported genes (BMP4, HNF4A and APOBR) and newly identified genes (SOCS4, GCH1, ATG14, RGS6, CYP7A1 and MAPK3), are involved in insulin metabolism or lipid metabolism, implicating the contribution of energy-metabolism-associated genes to the genetic basis of KET.
Body composition, plasma concentration of β-hydroxybutyrate (β-HB) and appetite-related hormones (active ghrelin, active glucagon-like peptide 1 [GLP-1], total peptide YY [PYY], cholecystokinin and insulin), and subjective feelings of appetite were measured at baseline, week 9 in ketosis, and week 13 out of ketosis.
Dairy cows with fatty liver or ketosis display decreased insulin sensitivity and defects in the insulin receptor substrate (IRS)/PI3K/AKT signaling pathway.
Most interestingly, several candidate genes, including previously reported genes (BMP4, HNF4A and APOBR) and newly identified genes (SOCS4, GCH1, ATG14, RGS6, CYP7A1 and MAPK3), are involved in insulin metabolism or lipid metabolism, implicating the contribution of energy-metabolism-associated genes to the genetic basis of KET.
PTEN negatively regulates the enzymes involved in hepatic gluconeogenesis and lipid synthesis, which suggests that PTEN may be a therapeutic target for ketosis and fatty liver in dairy cows.
Most interestingly, several candidate genes, including previously reported genes (BMP4, HNF4A and APOBR) and newly identified genes (SOCS4, GCH1, ATG14, RGS6, CYP7A1 and MAPK3), are involved in insulin metabolism or lipid metabolism, implicating the contribution of energy-metabolism-associated genes to the genetic basis of KET.
Most interestingly, several candidate genes, including previously reported genes (BMP4, HNF4A and APOBR) and newly identified genes (SOCS4, GCH1, ATG14, RGS6, CYP7A1 and MAPK3), are involved in insulin metabolism or lipid metabolism, implicating the contribution of energy-metabolism-associated genes to the genetic basis of KET.
The inverse dose-dependent relationship of osteocalcin and risk of ketosis was present across osteocalcin level quintiles (top quintile as the reference, adjusted odds ratio (95%CI) = 2.56 (0.80-8.17), 3.71 (0.90-15.29), 10.77 (2.63-44.15), 23.81 (4.32-131.17) per osteocalcin quintile respectively).
Most interestingly, several candidate genes, including previously reported genes (BMP4, HNF4A and APOBR) and newly identified genes (SOCS4, GCH1, ATG14, RGS6, CYP7A1 and MAPK3), are involved in insulin metabolism or lipid metabolism, implicating the contribution of energy-metabolism-associated genes to the genetic basis of KET.
Most interestingly, several candidate genes, including previously reported genes (BMP4, HNF4A and APOBR) and newly identified genes (SOCS4, GCH1, ATG14, RGS6, CYP7A1 and MAPK3), are involved in insulin metabolism or lipid metabolism, implicating the contribution of energy-metabolism-associated genes to the genetic basis of KET.
Reduced glycemia (p < 0.0001) and the associated changes in the regulation of ketosis (β-hydroxybutyrate) were accompanied by a metabolic shift (PPARβ, osteoprotegerin), suggesting the involvement of the different physiological systems tested.
Dairy cows with fatty liver or ketosis display decreased insulin sensitivity and defects in the insulin receptor substrate (IRS)/PI3K/AKT signaling pathway.
Reduced glycemia (p < 0.0001) and the associated changes in the regulation of ketosis (β-hydroxybutyrate) were accompanied by a metabolic shift (PPARβ, osteoprotegerin), suggesting the involvement of the different physiological systems tested.
Dairy cows with fatty liver or ketosis display decreased insulin sensitivity and defects in the insulin receptor substrate (IRS)/PI3K/AKT signaling pathway.
Dairy cows with fatty liver or ketosis display decreased insulin sensitivity and defects in the insulin receptor substrate (IRS)/PI3K/AKT signaling pathway.
The useful mnemonics for causes of high anion gap metabolic acidosis are the classic MUDPILES (representing Methanol, Uraemia, Diabetes, Paraldehyde, Iron (and Isoniazid), Lactate, Ethylene glycol, and Salicylate) and the more recently proposed GOLD MARK (Glycols [ethylene and propylene], Oxoproline, l-lactate, d-lactate, Methanol, Aspirin, Renal failure, and Ketoacidosis) as causes of the anion gap metabolic acidosis were all ruled out.
Most interestingly, several candidate genes, including previously reported genes (BMP4, HNF4A and APOBR) and newly identified genes (SOCS4, GCH1, ATG14, RGS6, CYP7A1 and MAPK3), are involved in insulin metabolism or lipid metabolism, implicating the contribution of energy-metabolism-associated genes to the genetic basis of KET.
Most interestingly, several candidate genes, including previously reported genes (BMP4, HNF4A and APOBR) and newly identified genes (SOCS4, GCH1, ATG14, RGS6, CYP7A1 and MAPK3), are involved in insulin metabolism or lipid metabolism, implicating the contribution of energy-metabolism-associated genes to the genetic basis of KET.
Our findings establish that specific targeting of hepatic PDKs with the PDK inhibitor PS10 is an effective therapeutic approach to maintaining glucose and lipid homeostasis in obesity and T2D, without the harmful ketoacidosis associated with systemic inhibition of PDKs.