Excess fat deposition and insulin resistance are considered the main risk factors for nonalcoholic fatty liver disease (NAFLD), and therefore, not surprisingly, the global prevalence of NAFLD increases in parallel with both obesity and type 2 diabetes. Although deterioration of bone homeostasis in patients with NAFLD is commonly observed, its etiology has not been fully elucidated yet. It was shown in several studies that bone tissue seems to be independently associated with NAFLD. A mechanistic perspective puts the liver at the center of mutual interdependencies obviously involving adipose tissue and muscles and also the bone matrix and bone cells, which are relatively novel. In this review, various pathophysiological mechanisms and possible mediating molecules that may interplay between NAFLD and bone tissue are described. Chronic inflammation, vitamin D3, growth hormone, insulin-like growth factor 1, osteopontin, fetuin-A, irisin, osteocalcin, and osteoprotegerin from osteoblasts have been proposed as mediators of mutual interactions among the skeleton, fatty tissue, and liver. Although to date there are still many issues that have not been elucidated, growing evidence suggests that screening and surveillance of bone mineral density in patients with NAFLD should be considered in future strategies and guidelines for NAFLD management.
3 August 2012 in Journal of Bone and Mineral Metabolism
Objective. The aim of the study was to determine the effect of α‐ketoglutarate on the blood lipid profile using a rat animal model with experimentally induced hypercholesterolaemia. Material and methods. The female and male (30/30) Wistar rats had ad libitum access to a diet containing cholesterol (1 %) and lard (10 %) throughout the entire experimental period (120 days). On day 60 of the study, both the females and the males were divided into three groups, the first receiving a mixture of drinking water adjusted to pH 4.6 using HCl (control), the other two (experimental groups) receiving a solution containing 0.01 M and 0.1 M α‐ketoglutarate (AKG) (pH adjusted to 4.6). Blood samples were taken on days 0, 30, 60 and 120. Results. The concentrations of total cholesterol, triglycerides, HDL and LDL, respectively, in the blood serum were estimated spectrophotometrically. During the entire experimental period the total cholesterol, triglycerides and LDL levels of the control rats increased, whereas that of HDL decreased. The serum concentrations of total cholesterol, LDL and triglycerides in both the experimental groups receiving AKG decreased (days 60 to 120) (p<0.05), while the HDL concentration tended to increase. The body gain in all groups receiving AKG was significantly lower than in the control group. Conclusions. These observations clearly prove that oral treatment with AKG can decrease the risk of hypercholesterolaemia developing and can lower the body weight. The relative concentrations of the plasma LDL and HDL changed to a more favourable ratio promoting good health.
2-Oxoglutaric acid (2-Ox), a precursor to hydroxyproline – the most abundant amino acid in bone collagen, exerts protective effects on bone development during different stages of organism development; however, little is known about the action of 2-Ox on cartilage. The aim of the present study was to elucidate the influence of dietary 2-Ox supplementation on the growth plate, articular cartilage and bone of growing rats. A total of twelve male Sprague–Dawley rats were used in the study. Half of the rats received 2-oxoglutarate at a dose of 0·75 g/kg body weight per d in their drinking-water. Body and organ weights were measured. Histomorphometric analyses of the cartilage and bone tissue of the femora and tibiae were conducted, as well as bone densitometry and peripheral quantitative computed tomography (pQCT). Rats receiving 2-Ox had an increased body mass (P< 0·001) and absolute liver weight (P= 0·031). Femoral length (P= 0·045) and bone mineral density (P= 0·014), overall thickness of growth plate (femurP= 0·036 and tibiaP= 0·026) and the thickness of femoral articular cartilage (P< 0·001) were also increased. 2-Ox administration had no effect on the mechanical properties or on any of the measured pQCT parameters for both bones analysed. There were also no significant differences in histomorphometric parameters of tibial articular cartilage and autofluorescence of femoral and tibial growth plate cartilage. Dietary supplementation with 2-Ox to growing rats exerts its effects mainly on cartilage tissue, having only a slight influence on bone. The effect of 2-Ox administration was selective, depending on the particular bone and type of cartilage analysed.