ABSTRACT
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ABSTRACT
BACKGROUND: Bariatric surgery remains the most effective treatment for reducing adiposity and eliminating type 2 diabetes; however, the mechanism(s) responsible have remained elusive. Peroxisome proliferator-activated receptors (PPAR) encompass a family of nuclear hormone receptors that upon activation exert control of lipid metabolism, glucose regulation and inflammation. Their role in adipose tissue following bariatric surgery remains undefined. MATERIALS AND METHODS: Subcutaneous adipose tissue biopsies and serum were obtained and evaluated from time of surgery and on postoperative day 7 in patients randomized to Roux-en-Y gastric bypass (n=13) or matched caloric restriction (n=14), as well as patients undergoing vertical sleeve gastrectomy (n=33). Fat samples were evaluated for changes in gene expression, protein levels, ß-oxidation, lipolysis and cysteine oxidation. RESULTS: Within 7 days, bariatric surgery acutely drives a change in the activity and expression of PPARγ and PPARδ in subcutaneous adipose tissue thereby attenuating lipid storage, increasing lipolysis and potentiating lipid oxidation. This unique metabolic alteration leads to changes in downstream PPARγ/δ targets including decreased expression of fatty acid binding protein (FABP) 4 and stearoyl-CoA desaturase-1 (SCD1) with increased expression of carnitine palmitoyl transferase 1 (CPT1) and uncoupling protein 2 (UCP2). Increased expression of UCP2 not only facilitated fatty acid oxidation (increased 15-fold following surgery) but also regulated the subcutaneous adipose tissue redoxome by attenuating protein cysteine oxidation and reducing oxidative stress. The expression of UCP1, a mitochondrial protein responsible for the regulation of fatty acid oxidation and thermogenesis in beige and brown fat, was unaltered following surgery. CONCLUSIONS: These results suggest that bariatric surgery initiates a novel metabolic shift in subcutaneous adipose tissue to oxidize fatty acids independently from the beiging process through regulation of PPAR isoforms. Further studies are required to understand the contribution of this shift in expression of PPAR isoforms to weight loss following bariatric surgery.
Subject(s)
Bariatric Surgery , Diabetes Mellitus, Type 2/prevention & control , Lipid Metabolism/physiology , Obesity, Morbid/surgery , PPAR delta/physiology , Subcutaneous Fat/metabolism , Adult , Fatty Acid-Binding Proteins/metabolism , Female , Gene Expression Regulation , Humans , Immunoblotting , Lipolysis/physiology , Male , Obesity, Morbid/metabolism , Treatment Outcome , Uncoupling Protein 2/metabolismABSTRACT
OBJECTIVE: To document an ovine disease attributed to the consumption of Lythrum hyssopifolia (lesser loosestrife). PROCEDURES: Historical and histological review of field and experimental cases. RESULTS: 1-20% mortality occurred in sheep flocks grazing paddocks where L. hyssopifolia was the predominant green vegetation. Well-documented disease outbreaks occurred in summer on nine farms across Victoria between 1974 and 2002. Liver damage occurred in all nine outbreaks, with kidney damage in at least eight. Hepatocyte necrosis was usually zonal to midzonal (zone 2) in the liver samples from four farms and periacinar (zone 3) in those from three farms, but some livers showed only single-cell necrosis. Multinucleate hepatocytes near necrotic areas were a feature in six cases. Proximal tubular epithelium appeared to be the primary renal target and brown granules were often present in renal tubules. Biochemical and histological evidence of liver and kidney damage was obtained from two sheep experimentally pen-fed harvested L. hyssopifolia. CONCLUSION: Chemicals in L. hyssopifolia are toxic to ovine hepatocytes and renal tubular epithelial cells.