Hepatokines and metabolism: Deciphering communication from the liver

Jensen-Cody, Sharon O.; Potthoff, Matthew J.

doi:10.1016/j.molmet.2020.101138

Cited by 145 publications

(98 citation statements)

References 271 publications

(225 reference statements)

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“…Further, the potential role of a vagal afferent signal communicating liver FAO and mitochondrial energy metabolism to the CNS may be reduced by the limited evidence of vagal afferent innervation of the liver parenchyma [ 65 ]. Alternatively, the systemic metabolic effects of the reduced liver FAO and mitochondrial energy metabolism may be due to altered hepatokine secretion (reviewed in [ 66 ]). Finally, the discussion of any vagal communication of decreased liver FAO and mitochondrial energy metabolism is further complicated by the possibility of the non-hepatocyte activation of the albumin promoter driven cre recombinase, particularly in the newborn rodent kidney and pancreas [ 67 ], and the rodent small intestine [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

Reduced Liver-Specific PGC1a Increases Susceptibility for Short-Term Diet-Induced Weight Gain in Male Mice

et al. 2021

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The central integration of peripheral neural signals is one mechanism by which systemic energy homeostasis is regulated. Previously, increased acute food intake following the chemical reduction of hepatic fatty acid oxidation and ATP levels was prevented by common hepatic branch vagotomy (HBV). However, possible offsite actions of the chemical compounds confound the precise role of liver energy metabolism. Herein, we used a hepatocyte PGC1a heterozygous (LPGC1a) mouse model, with associated reductions in mitochondrial fatty acid oxidation and respiratory capacity, to assess the role of liver energy metabolism in systemic energy homeostasis. LPGC1a male, but not female, mice had a 70% greater high-fat/high-sucrose (HFHS) diet-induced weight gain compared to wildtype (WT) mice (p < 0.05). The greater weight gain was associated with altered feeding behavior and lower activity energy expenditure during the HFHS diet in LPGC1a males. WT and LPGC1a mice underwent sham surgery or HBV to assess whether vagal signaling was involved in the HFHS-induced weight gain of male LPGC1a mice. HBV increased HFHS-induced weight gain (85%, p < 0.05) in male WT mice, but not LPGC1a mice. These data demonstrate a sex-specific role of reduced liver energy metabolism in acute diet-induced weight gain, and the need for a more nuanced assessment of the role of vagal signaling in short-term diet-induced weight gain.

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Section: Discussionmentioning

confidence: 99%

Reduced Liver-Specific PGC1a Increases Susceptibility for Short-Term Diet-Induced Weight Gain in Male Mice

et al. 2021

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“…The FGF21 signalling pathway begins with binding the co-receptors KLB (β-Klotho) and FGFR1 (FGF receptor 1), which forms an active FGF21/FGFR1/KLB receptor complex. Such a triple complex can phosphorylate ERK1/2 (extracellular signal-regulated kinases 1 and 2) and FRS2α (fibroblast growth factor receptor substrate 2 alpha) with multiple downstream targets [204]. The exact signalling cascade of FGF21 has not been fully resolved; it is known that in the liver, FGF21 expression is regulated by PPARα and could be also repressed by LXR [205,206].…”

Section: Pharmaceutical Strategies To Treat Nafld and Reduce Cvd Riskmentioning

confidence: 99%

Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases

Dabravolski

Bezsonov

Baig

et al. 2021

IJMS

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The prevalence of NAFLD (non-alcoholic fatty liver disease) is a rapidly increasing problem, affecting a huge population around the globe. However, CVDs (cardiovascular diseases) are the most common cause of mortality in NAFLD patients. Atherogenic dyslipidemia, characterized by plasma hypertriglyceridemia, increased small dense LDL (low-density lipoprotein) particles, and decreased HDL-C (high-density lipoprotein cholesterol) levels, is often observed in NAFLD patients. In this review, we summarize recent genetic evidence, proving the diverse nature of metabolic pathways involved in NAFLD pathogenesis. Analysis of available genetic data suggests that the altered operation of fatty-acid β-oxidation in liver mitochondria is the key process, connecting NAFLD-mediated dyslipidemia and elevated CVD risk. In addition, we discuss several NAFLD-associated genes with documented anti-atherosclerotic or cardioprotective effects, and current pharmaceutical strategies focused on both NAFLD treatment and reduction of CVD risk.

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“…Insulin-like growth factor 1 (IGF-1), previously known as somatomedin C [ 1 ] is a hepatokine responsible for proper metabolic function of cells and the metabolism of the whole organism [ 2 ]. This liver-derived factor can be found in the circulation, serving a mainly endocrine function, with its production mainly controlled by pituitary growth hormone (GH, somatotropin) [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Metabolic IGF-1 functions mostly involve the maintenance of normal insulin sensitivity, glucose uptake increase, plasma triglyceride decrease, and cholesterol level regulation [ 2 , 4 ]. Furthermore, hepatic glucose metabolism may directly induce the transcription of the IGF-1 gene [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Hypernutrition and hyperinsulinemia of obesity directly promote hepatic IGF-1 release and inhibit GH secretion [ 10 , 11 ]. Mechanisms of obesity formation and IR development [ 2 ], and the prevalence of metabolic syndrome (MetS), are not yet clear [ 12 , 13 ]. It is known that low levels of cIGF-1 predict the development of type 2 diabetes mellitus (DM II) and correlate with IR, increasing the risk of ischemic cardiovascular disease [ 7 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer

Kasprzak

2021

IJMS

118

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Colorectal cancer (CRC) is one of the most common aggressive carcinoma types worldwide, characterized by unfavorable curative effect and poor prognosis. Epidemiological data re-vealed that CRC risk is increased in patients with metabolic syndrome (MetS) and its serum components (e.g., hyperglycemia). High glycemic index diets, which chronically raise post-prandial blood glucose, may at least in part increase colon cancer risk via the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway. However, the underlying mechanisms linking IGF-1 and MetS are still poorly understood. Hyperactivated glucose uptake and aerobic glycolysis (the Warburg effect) are considered as a one of six hallmarks of cancer, including CRC. However, the role of insulin/IGF-1 signaling during the acquisition of the Warburg metabolic phenotypes by CRC cells is still poorly understood. It most likely results from the interaction of multiple processes, directly or indirectly regulated by IGF-1, such as activation of PI3K/Akt/mTORC, and Raf/MAPK signaling pathways, activation of glucose transporters (e.g., GLUT1), activation of key glycolytic enzymes (e.g., LDHA, LDH5, HK II, and PFKFB3), aberrant expression of the oncogenes (e.g., MYC, and KRAS) and/or overexpression of signaling proteins (e.g., HIF-1, TGF-β1, PI3K, ERK, Akt, and mTOR). This review describes the role of IGF-1 in glucose metabolism in physiology and colorectal carcinogenesis, including the role of the insulin/IGF system in the Warburg effect. Furthermore, current therapeutic strategies aimed at repairing impaired glucose metabolism in CRC are indicated.

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Hepatokines and metabolism: Deciphering communication from the liver

Cited by 145 publications

References 271 publications

Reduced Liver-Specific PGC1a Increases Susceptibility for Short-Term Diet-Induced Weight Gain in Male Mice

Reduced Liver-Specific PGC1a Increases Susceptibility for Short-Term Diet-Induced Weight Gain in Male Mice

Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases

Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer

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