Challenging dogma: is hepatic lipid accumulation in type 2 diabetes due to mitochondrial dysfunction?

Background & Aims: Insulin resistance is the real determinant of both Nonalcoholic fatty liver disease (NAFLD) and diabetes, and can facilitate the accumulation of triglycerides in the liver. Overexpression of hepassocin (HPS) increased the accumulation of hepatic fat and NAFLD activity scores (NAS) in mice. The aim of this study was to investigate the relationship between hepassocin and steatosis of the liver in diabetic patients with or without NAFLD in humans. Methods: The study enrolled 60 patients plus 20 healthy controls that were divided into 4 groups: Group I: included 20 patients who were diagnosed as diabetes mellitus type 2, Group II: included 20 patients who were diagnosed as nonalcoholic fatty liver disease (NAFLD), Group III: included 20 patients who were diagnosed as diabetes type 2 and NAFLD, and Group IV (control group): included 20 healthy person or controls who were matched in age and sex with patients group. All patients and controls were subjected to full history taking, thorough clinical examination, laboratory investigations including measurement of serum hepassocin in peripheral blood by ELISA technique. Results: There was a significant overexpression of serum hepassocin in patients with type 2 diabetes and NAFLD patients (Group 3) more than diabetic patients (Group 1) and even more than non-alcoholic fatty liver disease (Group 2). Conclusion: This study provides evidence that increased HPS may facilitate increased hepatic lipid accumulation with NAFLD and type 2 diabetes.

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Deletion of the diabetes candidate gene Slc16a13 in mice attenuates diet-induced ectopic lipid accumulation and insulin resistance

Communications Biology ◽

10.1038/s42003-021-02279-8 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Tina Schumann ◽

Jörg König ◽

Christian von Loeffelholz ◽

Daniel F. Vatner ◽

Dongyan Zhang ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Insulin Sensitivity ◽

Mitochondrial Respiration ◽

Lipid Accumulation ◽

Genome Wide Association Studies ◽

Alcoholic Fatty Liver ◽

Hepatic Insulin Sensitivity ◽

Hepatic Lipid

AbstractGenome-wide association studies have identified SLC16A13 as a novel susceptibility gene for type 2 diabetes. The SLC16A13 gene encodes SLC16A13/MCT13, a member of the solute carrier 16 family of monocarboxylate transporters. Despite its potential importance to diabetes development, the physiological function of SLC16A13 is unknown. Here, we validate Slc16a13 as a lactate transporter expressed at the plasma membrane and report on the effect of Slc16a13 deletion in a mouse model. We show that Slc16a13 increases mitochondrial respiration in the liver, leading to reduced hepatic lipid accumulation and increased hepatic insulin sensitivity in high-fat diet fed Slc16a13 knockout mice. We propose a mechanism for improved hepatic insulin sensitivity in the context of Slc16a13 deficiency in which reduced intrahepatocellular lactate availability drives increased AMPK activation and increased mitochondrial respiration, while reducing hepatic lipid content. Slc16a13 deficiency thereby attenuates hepatic diacylglycerol-PKCε mediated insulin resistance in obese mice. Together, these data suggest that SLC16A13 is a potential target for the treatment of type 2 diabetes and non-alcoholic fatty liver disease.

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