Expression profile of hepatic genes related to lipid homeostasis in LSR heterozygous mice contributes to their increased response to high-fat diet

Abstract

Perturbations of lipid homeostasis manifest as dyslipidemias and obesity, which are significant risk factors for atherosclerosis and diabetes. Lipoprotein receptors in the liver are key players in the regulation of lipid homeostasis, among which the hepatic lipolysis stimulated lipoprotein receptor, LSR, was recently shown to play an important role in the removal of lipoproteins from the circulation during the postprandial phase. Since heterozygous LSR+/- mice demonstrate moderate dyslipidemia and develop higher body weight gain in response to high-fat diet compared with littermate LSR+/+ controls, we questioned if LSR heterozygosity could affect genes related to hepatic lipid metabolism. A target-specific qPCR array for 84 genes related to lipid metabolism was performed on mRNA isolated from livers of 6 mo old female LSR+/- mice and LSR+/+ littermates following a 6 wk period on a standard (STD) or high-fat diet (60% kcal, HFD). Of the 84 genes studied, 32 were significantly downregulated in STD-LSR+/- mice compared with STD-LSR+/+, a majority of which were PPARα target genes involved in lipid metabolism and transport, and insulin and adipokine-signaling pathways. Of these 32 genes, 80% were also modified in HFD-LSR+/+, suggesting that STD-LSR+/- mice demonstrated a predisposition towards a "high-fat"-like profile, which could reflect dysregulation of liver lipid homeostasis. Since similar profiles of genes were affected by either LSR heterozygosity or by high-fat diet, this would suggest that LSR is a key receptor in regulating hepatic lipid homeostasis, and whose downregulation combined with a Western-type diet may increase predisposition to diet-induced obesity.

Association of Positive Hepatitis B Serology Markers with Risk and Behavior Factors in Kazakhstan Blood Donors: A Cross Sectional Study

“…Hepatic lipid accumulation involving genes related to cholesterol absorption and metabolism may also be associated with TLR2 gene overexpression [24]. Lipid homeostasis, manifesting as dyslipidemia, and initially observed obesity associated with lipoprotein receptor damage in the liver are considering the main factors for regulation of hepatic lipolysis [25]. Target gene analysis, using a whole genome expression profile among individuals with a high-fat diet, may offer not only a clearer picture of lipid metabolism in the liver [20] but may aid in understanding how HBV impacts the same pathway [26].…”

Garcinia cambogia Extract Increased Hepatic Levels of Lipolysis-Stimulated Lipoprotein Receptor and Lipids in Mice on Normal Diet

“…The lipolysisstimulated lipoprotein receptor (LSR) is an apoB,E receptor that binds with the highest affinity to TGRL and has been shown to contribute to the removal and endocytosis of these particles during the post-prandial phase [20,21]. Furthermore, LSR expression has been linked to transcriptional factors involved in fatty acid uptake, trafficking, and oxidation, as well as TG storage and lipolysis [22]. We recently reported that the epistatic interaction between LSR and APOE gene variants influences blood lipid profiles in a healthy cohort [23].…”

Leptin Downregulates Angulin-1 in Active Crohn’s Disease via STAT3

“…Angulin-1 could recruit tricellulin to the tTJ, and knockdown of angulin-1 leads to a decreased transepithelial resistance (TER) and an increased permeability to fluorescein and macromolecules up to 40 kDa [18], indicating that angulin-1-probably indirectly acting by the removal of tricellulin from the tTJ-was also essential for sustaining the epithelial barrier. To date, angulin-1 has been linked to lipid metabolic abnormality [19][20][21], Alzheimer's disease [22], and various cancers [23][24][25][26][27][28][29][30]. Akin to tricellulin, angulin-1 is also targeted by bacteria in order to breach the intestinal barrier [31,32].…”