linoleic-acid and Osteoporosis

Obesity and osteoporosis have grave consequences for human health, quality of life, and even the efficiency of the labor force and economy. However, these pathologies share a common cell progenitor, revealing a surprising target for drug research and development. Recent findings show that high adipocyte count in bone marrow is directly related to bone loss, as fat cells replace osteoblasts (or bone-forming cells). The objective of this review is to examine the importance of adipocyte apoptosis in the treatment of obesity and/or osteoporosis, with special emphasis on natural products as promising leads for drug development. We have induced in vivo adipocyte apoptosis, using leptin, ciliary neurotrophic factor (CNTF), beta adrenergic agonists and conjugated linoleic acid (CLA) in rodents. The results of leptin treatments on rats are suppressed food intake, reduced body weight, reduced body fat, adipocyte apoptosis, and elevated energy expenditure. Further, leptin treatment of leptin-deficient (ob/ob) mice increases endosteal bone formation and bone mineral density. Adipocyte apoptosis has also been induced in vitro using tumor necrosis factor-alpha (TNF-alpha), (-)-epigallocatechin gallate (EGCG) from Camellia sinensis and ajoene, from Allium sativum. Natural products have potential for inducing apoptosis of adipose tissue, inhibiting bone marrow adipogenesis and increasing the expression of osteogenic factors in bone, thereby yielding effective treatments for obesity and osteoporosis.

Topics: Adipocytes; Adrenergic beta-Agonists; Animals; Anti-Obesity Agents; Apoptosis; Bone Marrow; Catechin; Cell Differentiation; Ciliary Neurotrophic Factor; Disulfides; Flavonoids; Humans; Leptin; Linoleic Acid; Mesenchymal Stem Cells; Obesity; Osteoporosis; Plant Extracts; Sulfoxides; Tumor Necrosis Factor-alpha

Linoleic acid (LA; 18:2n-6) has been considered to promote low-grade chronic inflammation and adiposity. Studies show adiposity and inflammation are inversely associated with bone mass.. This study tested the hypothesis that decreasing the dietary ratio of LA to α-linolenic acid (ALA, 18:3n-3), while keeping ALA constant, mitigates high-fat diet (HF)-induced adiposity and bone loss.. Male C57BL/6 mice at 6 wk old were assigned to 4 treatment groups and fed 1 of the following diets ad libitum for 6 mo: a normal-fat diet (NF; 3.85 kcal/g and 10% energy as fat) with the ratio of the PUFAs LA to ALA at 6; or HFs (4.73 kcal/g and 45% energy as fat) with the ratio of LA to ALA at 10:1, 7:1, or 4:1, respectively. ALA content in the diets was kept the same for all groups at 1% energy. Bone structure, body composition, bone-related cytokines in serum, and gene expression in bone were measured. Data were analyzed using 1-factor ANOVA.. Compared with those fed the NF, mice fed the HFs had 19.6% higher fat mass (P < 0.01) and 13.5% higher concentration of serum tartrate-resistant acid phosphatase (TRAP) (P < 0.05), a bone resorption cytokine. Mice fed the HFs had 19.5% and 12.2% lower tibial and second lumbar vertebral bone mass, respectively (P < 0.01). Decreasing the dietary ratio of LA to ALA from 10 to 4 did not affect body mass, fat mass, serum TRAP and TNF-α, or any bone structural parameters.. These data indicate that decreasing the dietary ratio of LA to ALA from 10 to 4 by simply reducing LA intake does not prevent adiposity or improve bone structure in obese mice.

Topics: Adiposity; alpha-Linolenic Acid; Animals; Dietary Fats; Linoleic Acid; Male; Mice; Mice, Inbred C57BL; Obesity; Osteoporosis

Significance of dietary fatty acids on bone health is not clear, and the evidence is controversial. This study aimed to investigate the relationship between dietary polyunsaturated fatty acids (PUFAs) and bone mineral density (BMD) among elderly women.. Subjects (n=554) were drawn from the Kuopio OSTPRE Fracture Prevention Study. At baseline they filled a 3-day food record and a questionnaire on lifestyle factors, diseases and medications. BMD was measured at lumbar spine (L2-L4), femoral neck and total body by dual energy X-ray absorptiometry at baseline and after 3 years. The associations between dietary fatty acids and BMD were analyzed by a linear mixed model adjusting for potential dietary and non-dietary confounders.. Our findings suggested a positive relationship between the dietary PUFAs and BMD at lumbar spine and in total body but not at femoral neck. Further analyses revealed that these results were due to associations among the women without hormone therapy (HT) at baseline. Among them, the intake of total PUFAs as well the intakes of linoleic and linolenic acids and total n-3 and n-6 fatty acids were significantly associated with BMD at lumbar spine; P for trend over the quartiles ranged between 0.013 and 0.001. Similarly, significant associations were demonstrated for total body BMD and fatty acids with an exception of total PUFA. No significant associations were found among women with HT at baseline.. Our findings among elderly women without HT support the suggested beneficial effect of dietary PUFAs on bone health.

Topics: Absorptiometry, Photon; Aged; alpha-Linolenic Acid; Body Mass Index; Bone Density; Calcium, Dietary; Diet; Dietary Fats; Fatty Acids, Unsaturated; Female; Femur Neck; Humans; Linoleic Acid; Lumbar Vertebrae; Osteoporosis; Surveys and Questionnaires