Hepatic steatosis and <scp>PNPLA</scp>3 I148<scp>M</scp> variant are associated with serum <scp>F</scp>etuin‐<scp>A</scp> independently of insulin resistance

Rametta, Raffaela; Ruscica, Massimiliano; Dongiovanni, Paola; Macchi, Chiara; Fracanzani, Anna Ludovica; Steffani, Liliana; Fargion, Silvia; Magni, Paolo; Valenti, Luca

doi:10.1111/eci.12280

Cited by 25 publications

(22 citation statements)

References 31 publications

(74 reference statements)

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“…Circulating fetuin-A levels have been associated with severity of liver steatosis, independently of insulin resistance, and with non-alcoholic steatohepatitis [45,46]. Our results showed a strong association between fetuin-A levels and changes in liver fat content.…”

Section: Discussionsupporting

confidence: 55%

A heterogeneous response of liver and skeletal muscle fat to the combination of a Paleolithic diet and exercise in obese individuals with type 2 diabetes: a randomised controlled trial

et al. 2018

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Aims/hypothesis The aim of the study was to investigate ectopic fat deposition and insulin sensitivity, in a parallel single-blinded randomised controlled trial, comparing Paleolithic diet alone with the combination of Paleolithic diet and exercise in individuals with type 2 diabetes. Methods Thirty-two individuals with type 2 diabetes with BMI 25-40 kg/m 2 and 30-70 years of age followed a Paleolithic diet ad libitum for 12 weeks. In addition, study participants were randomised by computer program to either supervised combined exercise training (PD-EX group) or standard care exercise recommendations (PD group). Staff performing examinations and assessing outcomes were blinded to group assignment. Thirteen participants were analysed in each group: hepatic and peripheral insulin sensitivity were measured using the hyperinsulinaemic-euglycaemic clamp technique combined with [6, H 2 ]glucose infusion, and liver fat was assessed by proton magnetic resonance spectroscopy; both analyses were secondary endpoints. Intramyocellular lipid (IMCL) content was measured by magnetic resonance spectroscopy as a secondary analysis. All examinations were performed at Umeå University Hospital, Umeå, Sweden. Results Both study groups showed a median body weight loss of 7 kg. Fat mass decreased by 5.7 kg in the PD group and by 6.5 kg in the PD-EX group. Maximum oxygen uptake increased in the PD-EX group only. Liver fat showed a consistent reduction (74% decrease) in the PD group, while the response in the PD-EX group was heterogeneous (p < 0.05 for the difference between groups). IMCL content of the soleus muscle decreased by 40% in the PD group and by 22% in the PD-EX group (p < 0.05 for the difference between groups). Both groups improved their peripheral and adipose tissue insulin sensitivity, but not their hepatic insulin sensitivity. Plasma fetuin-A decreased by 11% in the PD group (p < 0.05) and remained unchanged in the PD-EX group. Liver fat changes during the intervention were correlated with changes in fetuin-A (r S = 0.63, p < 0.01). Participants did not report any important adverse events caused by the intervention. Conclusions/interpretation A Paleolithic diet reduced liver fat and IMCL content, while there was a tissue-specific heterogeneous response to added exercise training.

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Section: Discussionsupporting

confidence: 55%

A heterogeneous response of liver and skeletal muscle fat to the combination of a Paleolithic diet and exercise in obese individuals with type 2 diabetes: a randomised controlled trial

et al. 2018

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“…Fetuin-A does not seem to be directly regulated by inflammation, and no correlation was observed between hepatic inflammation and serum levels in patients with NAFLD [199]. …”

Section: Liver-released Compoundsmentioning

confidence: 99%

“…Increased Fetuin-A has been reported in obese children and lean adults with NAFLD [199,200]. In patients with NAFLD, Fetuin-A levels were associated with the severity of steatosis, were influenced by genetic risk factors for hepatic fat accumulation and also correlated with insulin resistance and metabolic syndrome features [199].…”

Section: Liver-released Compoundsmentioning

confidence: 99%

Pathophysiology of Non Alcoholic Fatty Liver Disease

Petta

Gastaldelli

Rebelos

et al. 2016

IJMS

Self Cite

142

105

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The physiopathology of fatty liver and metabolic syndrome are influenced by diet, life style and inflammation, which have a major impact on the severity of the clinicopathologic outcome of non-alcoholic fatty liver disease. A short comprehensive review is provided on current knowledge of the pathophysiological interplay among major circulating effectors/mediators of fatty liver, such as circulating lipids, mediators released by adipose, muscle and liver tissues and pancreatic and gut hormones in relation to diet, exercise and inflammation.

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“…Circulating levels of fetuin-A are elevated in several pathological conditions including obesity, type 2 diabetes, and NAFLD [17]. Because elevated levels of fetuin-A are positively correlated with hepatic fat contents, it has been suggested as a marker of simple hepatic steatosis [18,19]. Lower levels of adiponectin and higher levels of fetuin-A may mediate the pathophysiological processes of metabolic diseases, with fetuin-A having an inverse relationship with adiponectin [20,21].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…Fetuin-A, a main hepatokine, stimulates the production of pro-inflammatory cytokines, and interferes with insulin signaling in part by acting as an endogenous ligand of the Toll-like receptor [38]. Fetuin-A is considered as a biomarker of chronic inflammatory diseases and hepatic fat contents [18,19,39]. Fetuin-A overexpression is accompanied by the increased levels and activation of NF-κB [40].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Involvement of resveratrol in crosstalk between adipokine adiponectin and hepatokine fetuin-A in vivo and in vitro

Lee

Lim

Yang

2015

The Journal of Nutritional Biochemistry

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Hepatic steatosis and PNPLA3 I148M variant are associated with serum Fetuin‐A independently of insulin resistance

Abstract: Liver fat accumulation and the I148M variant of PNPLA3 are associated with serum Fetuin-A levels independently of insulin resistance. Fetuin-A may be implicated in the pathogenesis of metabolic complications associated with NAFLD.

Cited by 25 publications

References 31 publications

A heterogeneous response of liver and skeletal muscle fat to the combination of a Paleolithic diet and exercise in obese individuals with type 2 diabetes: a randomised controlled trial

A heterogeneous response of liver and skeletal muscle fat to the combination of a Paleolithic diet and exercise in obese individuals with type 2 diabetes: a randomised controlled trial

Pathophysiology of Non Alcoholic Fatty Liver Disease

Involvement of resveratrol in crosstalk between adipokine adiponectin and hepatokine fetuin-A in vivo and in vitro

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