Influence of NAFLD and bariatric surgery on hepatic and adipose tissue mitochondrial biogenesis and respiration

Abstract

Impaired mitochondrial oxidative phosphorylation (OXPHOS) in liver tissue has been hypothesised to contribute to the development of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease (NAFLD). It is unknown whether OXPHOS capacities in human visceral (VAT) and subcutaneous adipose tissue (SAT) associate with NAFLD severity and how hepatic OXPHOS responds to improvement in NAFLD. In biopsies sampled from 62 patients with obesity undergoing bariatric surgery and nine control subjects without obesity we demonstrate that OXPHOS is reduced in VAT and SAT while increased in the liver in patients with obesity when compared with control subjects without obesity, but this was independent of NAFLD severity. In repeat liver biopsy sampling in 21 patients with obesity 12 months after bariatric surgery we found increased hepatic OXPHOS capacity and mitochondrial DNA/nuclear DNA content compared with baseline. In this work we show that obesity has an opposing association with mitochondrial respiration in adipose- and liver tissue with no overall association with NAFLD severity, however, bariatric surgery increases hepatic OXPHOS and mitochondrial biogenesis.

Loss of mitochondrial adaptation associates with deterioration of mitochondrial turnover and structure in obesity-related fatty liver disease

“…There is now growing evidence for different adaptive changes of hepatic mitochondrial capacity in NAFL, NASH and fibrosis [14,16,19]. The present study confirms upregulation of TCA-and βoxidation-linked mitochondrial respiration in obese humans with NAFL, but not NASH [14].…”

“…A recent high-resolution respirometry study found that only a group with definite histopathological NASH exhibited lower fatty acid oxidation, when compared to NAFL or borderline NASH groups [17]. Liver respiration was also nominally highest in NAFL, intermediate in NASH and nonsteatotic obesity and lowest in non-steatotic humans in another study [16]. The present study extends these findings by showing an inverse relationship between mitochondrial capacity and mitochondrial diameter across all obese groups combined, suggesting that mitochondrial elongation reflects low respiratory competence.…”

“…Comprehensive multiomics analyses of human liver biopsies and metabolic flux data also showed adaptation of mitochondrial metabolism in the presence of increased amount of liver fat [15]. Recent studies generally confirmed and extended these studies in other cohorts [16,17].…”

BaoShenTongLuo formula protects against podocyte injury by regulating AMPK-mediated mitochondrial biogenesis in diabetic kidney disease

“…Increasing numbers of publications have reported that impaired mitochondrial functions are involved in various diseases, such as diabetes, Parkinson's disease, and nonalcoholic fatty liver disease [ 41 – 44 ]. Mitochondrial biogenesis is the process by which new mitochondria are formed in tissues and cells, and this process is activated by different signals in response to internal and external environmental stimuli [ 45 ].…”

BaoShenTongLuo formula protects against podocyte injury by regulating AMPK-mediated mitochondrial biogenesis in diabetic kidney disease.

“…Increasing numbers of publications have reported that impaired mitochondrial functions are involved in various diseases, such as diabetes, Parkinson's disease, and nonalcoholic fatty liver disease (41)(42)(43)(44).…”