Intestinal metabolism of fatty acids

1. The effect of concentration on the oxidation and incorporation into lipids of lauric acid and linoleic acid by rings of rat small intestine has been studied in vitro. 2. In the absence of glucose, the oxidation of lauric acid in the range 0.01-5.0mm showed a maximum at 0.1mm. In the presence of glucose the maximum was at 0.5mm. The oxidation of linoleic acid in the presence of glucose increased throughout the concentration range 0.01-5.0mm. 3. The incorporation of lauric acid into lipids was maximal at 0.5-0.6mm in the presence of glucose, but at 10mm in the absence of glucose. At 0.8mm-lauric acid, in the presence of glucose, over 75% of the incorporated lauric acid was in triglycerides, but at 10mm they only contained 30%. The incorporation of glucose carbon into glycerides paralleled the incorporation of lauric acid. 4. In the range 0.01-2.5mm-linoleic acid the quantity incorporated into lipids increased. In the range 0.01-0.4mm linoleic acid was incorporated predominantly into triglycerides, but between 0.4 and 1.0mm most was in diglycerides, and between 2.5 and 5.0mm most was in monoglycerides. 5. The relationship of fatty acid concentration to the mechanism of absorption is discussed, together with the correlation between the distribution of the absorbed fatty acids within the tissue lipids and the lipase activity of intestinal mucosa.     

A comparison of procedures to determine free fatty acids in rat heart

The level of free fatty acids in intact tissues has been found to be low but is known to rise in proportion to the extent of autolysis. Therefore, the high levels of free fatty acid reported in the cardiac lipids of rats fed rapeseed oil were reinvestigated using two different procedures for homogenization. Quick freezing and pulverization at dry ice temperature followed by lipid extraction was found to give lower values of free fatty acids (200 microgram/g of wet heart tissue) than the more commonly used technique of employing rotating blade-type homogenizers (greater than 1700 microgram/g of wet heart tissue). The amount of diglycerides was found to be 3 times greater when the latter method was used. The high levels of free fatty acid and diglyceride suggest that extensive autolysis occurs during homogenization with a rotating blade-type homogenizer. Freezing and pulverization at dry ice temperature is therefore recommended for determining intact lipid classes in rat heart.     

Excretion and metabolism of desogestrel in healthy postmenopausal women

The metabolism of desogestrel (13-ethyl-11-methylene-18,19-dinor-17-pregn-4-en-20-yn-17-ol), a progestagen used in oral contraceptives and hormone replacement therapy, was studied in vivo after a single oral administration of 150 μg [¹⁴C]-labeled desogestrel and 30 μg ethinylestradiol under steady state conditions to healthy postmenopausal women. After this oral administration, desogestrel was extensively metabolized. The dosed radioactivity was predominantly (60%) excreted via urine, while about 35% was excreted via the feces. Desogestrel was metabolized mainly at the C3-, C5-, C6- and C13-CH₂CH₃ positions. At the C3-position, the 3-keto moiety was found and in addition, 3β-hydroxy and 3-hydroxy groups were observed in combination with a reduced Δ⁴-double bond (5-H). Hydroxy groups were introduced at the C6- (6β-OH), the C13-ethyl (C13-CH₂CH₂OH) and possibly the C15- (15-OH) position of desogestrel. Conjugation of the 3-hydroxy moiety with sulfonic acid and conjugation with glucuronic acid were also major metabolic routes found for desogestrel in postmenopausal women. The 3-keto metabolite of desogestrel (the biologically active metabolite) was the major compound present in plasma at least up to 24 h after administration of the radioactive dose. Species comparison of the metabolic routes of desogestrel after oral administration indicates that in rats and dogs desogestrel is also mainly metabolized at the C3-position, similar to what is now found for postmenopausal women. Most other metabolic routes of desogestrel were found to differ between species. Finally, major metabolic routes found in the present study in postmenopausal women are in line with outcome of previous in vitro metabolism studies with human liver tissue (microsomes and postmitochondrial liver fractions) and intestinal mucosa.     

Long-chain polyunsaturated fatty acids and the regulation of bone metabolism

The role of prostaglandin E2 (PGE2) in the regulation of bone remodeling is well established. There is increasing evidence that various long-chain polyunsaturated fatty acids (LCPUFAs), as well as nonprostanoid LCPUFA metabolites, also have critical roles in regulating bone metabolism and may have therapeutic potential in the management of postmenopausal osteoporosis. Although only the 18-carbon precursors for the n-3 and n-6 LCPUFAs are deemed "dietary essential," the ability of the body to convert these precursor fatty acids into the more highly unsaturated 20- and 22-carbon LCPUFAs decreases with aging, menopause, and various lifestyle factors (e.g., smoking). Increasing dietary LCPUFA intake increases tissue and blood LCPUFA concentrations, as well as the concentrations of their metabolites. Modification of dietary LCPUFA content, particularly increasing the intake of n-3 LCPUFAs, has been shown to minimize the decline in bone mass caused by menopause in women and ovariectomy in animal models. This review summarizes findings from both in vivo and in vitro studies and outlines the effects of LCPUFAs and their metabolites on calcium balance, osteoblastogenesis, osteoclastogenesis, and osteoblast and osteoclast function.     

Nutritional status and intermediate chain-length fatty acids influence the conservation of essential fatty acids in the milk of northern Nigerian women

The milk of 89 women in northern Nigeria was analyzed for the fatty acid composition of the total milk lipids, and assessed for the effect nutritional status has on the conservation of essential and non-essential fatty acids when the proportions of C(10)-C(14)fatty acids are increased. The women were stratified on the basis of their body mass index, and calculations were made to estimate the effects of a 3.3-fold increase in the proportion of C(10)-C(14)fatty acids on the proportion of alpha-linolenic acid, docosahexaenoic acid, linoleic acid and arachidonic in total milk lipids. In the well-nourished group (group III, body mass index >23 kg/m(2)), the critical n-3 and n-6 fatty acids were not conserved, while in poorly nourished women (group I, body mass index <19 kg/m(2)), marked conservation of alpha-linolenic acid, docosahexaenoic acid, arachidonic acid, and palmitic acid was seen. Poor nutritional status of the mother appears to promote selective retention of critical essential and non-essential fatty acids in the milk lipid fraction.