Liver-derived FGF21 is essential for full adaptation to ketogenic diet but does not regulate glucose homeostasis

Watanabe, Mikiko; Singhal, Garima; Fisher, Ffolliott M.; Beck, Thomas C.; Morgan, Donald A.; Socciarelli, Fabio; Mather, Marie L.; Risi, Renata; Bourke, Jared; Rahmouni, Kamal; McGuinness, Owen P.; Flier, Jeffrey S.; Maratos–Flier, Eleftheria

doi:10.1007/s12020-019-02124-3

Cited by 30 publications

(30 citation statements)

References 55 publications

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“…Long-term administration of FGF-21 prevents chemically induced hepatocarcinogenesis in mice [37]. However, FGF-21 is known to be expressed in several tissues, including those of the liver, fat, and pancreas [38]. Serum FGF-21 levels are affected by various tissues expressing FGF-21, and, therefore, FGF-21 was not identified as an independent prognostic factor in patients with HCC.…”

Section: Discussionmentioning

confidence: 99%

Impact of Decorin on the Physical Function and Prognosis of Patients with Hepatocellular Carcinoma

Kawaguchi

Yoshio

Sakamoto

et al. 2020

JCM

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The outcome of patients with hepatocellular carcinoma (HCC) is still poor. Decorin is a small leucine-rich proteoglycan, which exerts antiproliferative and antiangiogenic properties in vitro. We aimed to investigate the associations of decorin with physical function and prognosis in patients with HCC. We enrolled 65 patients with HCC treated with transcatheter arterial chemoembolization (median age, 75 years; female/male, 25/40). Serum decorin levels were measured using enzyme-linked immunosorbent assays; patients were classified into the High or Low decorin groups by median levels. Associations of decorin with physical function and prognosis were evaluated by multivariate correlation and Cox regression analyses, respectively. Age and skeletal muscle indices were not significantly different between the High and Low decorin groups. In the High decorin group, the 6-min walking distance was significantly longer than the Low decorin group and was significantly correlated with serum decorin levels (r = 0.2927, p = 0.0353). In multivariate analysis, the High decorin group was independently associated with overall survival (hazard ratio 2.808, 95% confidence interval 1.016–8.018, p = 0.0498). In the High decorin group, overall survival rate was significantly higher than in the Low decorin group (median 732 days vs. 463 days, p = 0.010). In conclusion, decorin may be associated with physical function and prognosis in patients with HCC.

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Section: Discussionmentioning

confidence: 99%

Impact of Decorin on the Physical Function and Prognosis of Patients with Hepatocellular Carcinoma

Kawaguchi

Yoshio

Sakamoto

et al. 2020

JCM

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“…20 Preclinical studies report a significant reduction in the cerebral blood flow, reduced glucose utilization similar to metabolic encephalopathies, and embryonic growth retardation, 77 but it should be noted that the KD given to rodent models is highly insufficient in protein and not comparable to a KD usually prescribed to human beings, making results scarcely translational. 78 Lactation ketoacidosis is a well-described condition in cows, and it occurs as the high demand of glucose leads to fat mobilization, ketosis and ultimately acidosis under certain circumstances. Lactation ketoacidosis is rarely described to happen spontaneously in women, but a few case reports show an increased risk when KD is a precipitating factor.…”

Section: Pregnancy and Breastfeedingmentioning

confidence: 99%

“…84 In fact, nutritional ketosis and weight loss are only observed in rats and mice when both protein and carbohydrate intake are reduced to less than 10%. 78…”

Section: Cardiac Arrhythmiasmentioning

confidence: 99%

“…97 The concomitant consumption of a KD exacerbates the risk, and it is therefore to be recommend against the prescription of a KD to those with a history of alcohol and substance abuse where relapse seems possible, especially in the absence of adequate support. Noteworthy, a ketogenic diet seems to be effective in suppressing alcohol cravings both at a preclinical level and in subjects with obesity, 98,99 although it should be kept in mind that the physiology underlying such association might be very different across species, as the link in rodent models seems to be an elevation in Fibroblast Growth Factor 21 levels, 78,100 whereas such elevation following a ketogenic diet is not observed in human beings. 101…”

Section: Frail Elderly Patients History Of Mental Disorders and Sumentioning

confidence: 99%

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Scientific evidence underlying contraindications to the ketogenic diet: An update

et al. 2020

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Summary First identified as a feasible treatment for intractable epilepsy, the ketogenic diet (KD) has recently gained popularity thanks to growing evidence on applications such as weight loss, most importantly, but also NAFLD, cancer, neurologic conditions and chronic pain. As with any treatment, whether pharmacologic or not, the KD might not be an appropriate intervention for every individual, and a number of contraindications have been proposed, now deeply rooted into clinical practice, excluding de facto many patients that could benefit from its use. However, many of these concerns were expressed due to the absence of clinical studies conducted on fragile populations, and an assessment of lately emerged evidence relative to KD safety is currently lacking and much needed. We herein provide a critical revision of the literature behind each safety alert, in order to guide through the treatment options in the case of subjects with an indication to the KD and a borderline safe situation. Based on available evidence, the possible use of this diet as a therapeutic intervention should be assessed on a patient‐to‐patient basis by adequately skilled medical doctors, keeping in mind current recommendations, but reading them through the knowledge of the current state of the art.

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“…Thyroid hormones followed the same pathway, and since then, the scientific community has tried to find the "perfect" stimulant. Fibroblast growth factor 21 was recently tested on human beings, as it was shown to induce BAT activation and browning of white adipose tissue in rodents, with a net effect of increased energy expenditure [160,161]. However, studies on primates and human subjects quickly proved that the physiology of energy metabolism is very different across species, and the same effect could not be replicated in men or women.…”

Section: Increased Energy Expenditure As Purported Mechanisms Of Actionmentioning

confidence: 99%

Current Evidence to Propose Different Food Supplements for Weight Loss: A Comprehensive Review

et al. 2020

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The use of food supplements for weight loss purposes has rapidly gained popularity as the prevalence of obesity increases. Navigating through the vast, often low quality, literature available is challenging, as is providing informed advice to those asking for it. Herein, we provide a comprehensive literature revision focusing on most currently marketed dietary supplements claimed to favor weight loss, classifying them by their purported mechanism of action. We conclude by proposing a combination of supplements most supported by current evidence, that leverages all mechanisms of action possibly leading to a synergistic effect and greater weight loss in the foreseen absence of adverse events. Further studies will be needed to confirm the weight loss and metabolic improvement that may be obtained through the use of the proposed combination.

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Liver-derived FGF21 is essential for full adaptation to ketogenic diet but does not regulate glucose homeostasis

Cited by 30 publications

References 55 publications

Impact of Decorin on the Physical Function and Prognosis of Patients with Hepatocellular Carcinoma

Impact of Decorin on the Physical Function and Prognosis of Patients with Hepatocellular Carcinoma

Scientific evidence underlying contraindications to the ketogenic diet: An update

Current Evidence to Propose Different Food Supplements for Weight Loss: A Comprehensive Review

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