Diet and Gastrointestinal Bypass–Induced Weight Loss: The Roles of Ghrelin and Peptide YY

OBJECTIVE-Bariatric surgery causes durable weight loss. Gut hormones are implicated in obesity pathogenesis, dietary failure, and mediating gastrointestinal bypass (GIBP) surgery weight loss. In mice, we determined the effects of diet-induced obesity (DIO), subsequent dieting, and GIBP surgery on ghrelin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). To evaluate PYY's role in mediating weight loss post-GIBP, we undertook GIBP surgery in PyyKO mice.RESEARCH DESIGN AND METHODS-Male C57BL/6 mice randomized to a high-fat diet or control diet were killed at 4-week intervals. DIO mice underwent switch to ad libitum low-fat diet (DIO-switch) or caloric restriction (CR) for 4 weeks before being killed. PyyKO mice and their DIO wild-type (WT) littermates underwent GIBP or sham surgery and were culled 10 days post-operatively. Fasting acyl-ghrelin, total PYY, active GLP-1 concentrations, stomach ghrelin expression, and colonic Pyy and glucagon expression were determined. Fasting and postprandial PYY and GLP-1 concentrations were assessed 30 days postsurgery in GIBP and sham pair-fed (sham.PF) groups.RESULTS-DIO progressively reduced circulating fasting acyl-ghrelin, PYY, and GLP-1 levels. CR and DIO-switch caused weight loss but failed to restore circulating PYY to weight-appropriate levels. After GIBP, WT mice lost weight and exhibited increased circulating fasting PYY and colonic Pyy and glucagon expression. In contrast, the acute effects of GIBP on body weight were lost in PyyKO mice. Fasting PYY and postprandial PYY and GLP-1 levels were increased in GIBP mice compared with sham.PF mice.CONCLUSIONS-PYY plays a key role in mediating the early weight loss observed post-GIBP, whereas relative PYY deficiency during dieting may compromise weight-loss attempts. Diabetes 60:810-818, 201

Enhancing liver mitochondrial fatty acid oxidation capacity in obese mice improves insulin sensitivity independently of hepatic steatosis

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LKB1 as a Gatekeeper of Hepatocyte Proliferation and Genomic Integrity during Liver Regeneration

Comment inLKB1: Controlling Quiescence and Genomic Integrity at Home. [Trends Endocrinol Metab. 2018]International audienceLiver kinase B1 (LKB1) is involved in several biological processes and is a key regulator of hepatic metabolism and polarity. Here, we demonstrate that the master kinase LKB1 plays a dual role in liver regeneration, independently of its major target, AMP-activated protein kinase (AMPK). We found that the loss of hepatic Lkb1 expression promoted hepatocyte proliferation acceleration independently of metabolic/energetic balance. LKB1 regulates G0/G1 progression, specifically by controlling epidermal growth factor receptor (EGFR) signaling. Furthermore, later in regeneration, LKB1 controls mitotic fidelity. The deletion of Lkb1 results in major alterations to mitotic spindle formation along the polarity axis. Thus, LKB1 deficiency alters ploidy profile at late stages of regeneration. Our findings highlight the dual role of LKB1 in liver regeneration, as a guardian of hepatocyte proliferation and genomic integrity

Novel Grb14-Mediated Cross Talk between Insulin and p62/Nrf2 Pathways Regulates Liver Lipogenesis and Selective Insulin Resistance

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Alternative splicing of hepatitis B virus: A novel virus/host interaction altering liver immunity

Background & aims-Hepatitis B virus (HBV) RNA can undergo alternative splicing but the relevance of this post-transcriptional regulation remains elusive. Here, the mechanism of HBV alternative splicing regulation and its impact on liver pathogenesis were investigated. Methods-HBV RNA-interacting proteins were identified by RNA pull-down combined to mass spectrometry analysis. HBV splicing regulation was investigated in chemically and surgically induced liver damage in whole HBV genome transgenic mice and in hepatoma cells. Viral an

Combined Bacterial Meningitis and Infective Endocarditis: When Should We Search for the Other When Either One is Diagnosed?

Auteurs groupes collaboratifs AEPEI study group & the COMBAT study groupInternational audienc