Mitochondrial respiration in subcutaneous and visceral adipose tissue from patients with morbid obesity

Abstract

Adipose tissue exerts important endocrine and metabolic functions in health and disease. Yet the bioenergetics of this tissue is not characterized in humans and possible regional differences are not elucidated. Using high resolution respirometry, mitochondrial respiration was quantified in human abdominal subcutaneous and intra-abdominal visceral (omentum majus) adipose tissue from biopsies obtained in 20 obese patients undergoing bariatric surgery. Mitochondrial DNA (mtDNA) and genomic DNA (gDNA) were determined by the PCR technique for estimation of mitochondrial density. Adipose tissue samples were permeabilized and respirometric measurements were performed in duplicate at 37• C. Substrates (glutamate (G) + malate (M) + octanoyl carnitine (O) + succinate (S)) were added sequentially to provide electrons to complex I + II. ADP ( D ) for state 3 respiration was added after GM. Uncoupled respiration was measured after addition of FCCP. Visceral fat contained more mitochondria per milligram of tissue than subcutaneous fat, but the cells were smaller. Robust, stable oxygen fluxes were found in both tissues, and coupled state 3 (GMOS D ) and uncoupled respiration were significantly (P < 0.05) higher in visceral (0.95 ± 0.05 and 1.15 ± 0.06 pmol O 2 s −1 mg −1 , respectively) compared with subcutaneous (0.76 ± 0.04 and 0.98 ± 0.05 pmol O 2 s −1 mg −1 , respectively) adipose tissue. Expressed per mtDNA, visceral adipose tissue had significantly (P < 0.05) lower mitochondrial respiration. Substrate control ratios were higher and uncoupling control ratio lower (P < 0.05) in visceral compared with subcutaneous adipose tissue. We conclude that visceral fat is bioenergetically more active and more sensitive to mitochondrial substrate supply than subcutaneous fat. Oxidative phosphorylation has a higher relative activity in visceral compared with subcutaneous adipose tissue.

All-trans retinoic acid induces oxidative phosphorylation and mitochondria biogenesis in adipocytes

“…Interestingly, whereas multilocular, UCP1-expressing brown adipocyte-like cells (i.e., beige/ BRITE adipocytes) are readily induced in vivo upon ATRA by guest, on www.jlr.org treatment in the subcutaneous (inguinal) WAT of mice, in the visceral depots ATRA treatment increases OXPHOS capacity without inducing the appearance of such cells [this work and ( 11 )]. Subcutaneous WAT is more prone to browning than visceral WAT ( 43 ), whereas rodent and human visceral adipocytes contain more mitochondria and have higher oxidative capacity as compared with subcutaneous adipocytes ( 44,45 ). It would appear, therefore, that ATRA treatment is able to potentiate differential intrinsic capacities of each type of fat depot, thus enhancing energy expenditure by an UCP1-dependent mechanism in subcutaneous WAT and by an UCP1-independent mechanism in the visceral WAT depots.…”

Metformin-treated patients with type 2 diabetes have normal mitochondrial complex I respiration

“…Quantification of genomic and mitochondrial DNA (mtDNA) was measured as described by Kraunsoe et al [19] Blood samples were collected in chilled tubes and immediately centrifuged for 10 min (2,500g; 4°C). The plasma fraction was collected and stored at −20°C or −80°C prior to analysis.…”

Impaired Bioenergetics in Clinical Medicine: A Target to Tackle

“…Research in humans on hepatic energy metabolism under conditions of type 2 diabetes mellitus, insulin resistance and non-alcoholic fatty liver disease revealed reduced HEPs content, decreased ATP recovery and altered flux through ATP synthase (for review see Koliaki and Roden (2013)). Mitochondrial transmembrane potential, inorganic phosphate utilization (indicative of ATP synthase capacity), and the activities of respiratory chain complexes I-IV in subcutaneous white adipose tissue were all reduced in obese and type 2 diabetes mellitus patients compared to those in control subjects (Kraunsøe et al 2010;Chattopadhyay et al 2011). Obesity and insulin resistance were also associated with impaired bioenergetics following exercise in overweight-to-obese children (Slattery et al 2014;Wells et al 2017) and adults (Valkovič et al 2013), as evaluated via slower mitochondrial oxidative capacity recovery in the skeletal muscle.…”