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PubMed1995

Factor VII coagulant activity in relation to serum lipoproteins and dietary fat in middle-aged men.

The associations of serum lipoproteins and habitual diet to factor VII coagulant activity (FVIIc) were analysed in 119 middle-aged men. FVIIc was measured by one-stage clotting assay, cholesterol and triglycerides enzymatically, serum apolipoproteins (apo) immunoturbidimetrically and habitual diet using four-day food records. ApoB, cholesterol, triglycerides, apoA-II, LDL cholesterol and dietary fat correlated directly to FVIIc (p < 0.001). In multivariate analysis apoB, dietary fat and apoA-II explained 35.3% of the variance in FVIIc. In the lowest apoB tertile FVIIc was increased only when fat intake was high (> 38 E%), in the middle tertile FVIIc increased gradually from low to high fat intake, whereas in the highest apoB tertile FVIIc was not related to dietary fat (p = 0.038 for age-adjusted interaction). The present data demonstrate a direct relation between apoB and FVIIc in middle-aged men. Low fat diet seem to associate to decreased FVIIc especially in subjects in the lower end of the apoB distribution.

Antigens↗
PubMed2006

Plasma C-reactive protein concentration is not affected by isocaloric dietary fat reduction.

OBJECTIVE: There is a strong correlation between plasma C-reactive protein (CRP) concentration and risk of cardiovascular death. Low-fat diets have been recommended for maintenance of cardiovascular health, and it is known that a low-fat diet associated with weight loss lowers CRP concentration. However, it remains unclear whether dietary fat has an effect independent from weight change on markers of inflammation. METHODS: Sixteen overweight subjects who were 46 +/- 14 y old were placed on a weight-maintaining baseline diet consisting of 35% fat, 45% carbohydrate, and 20% energy as protein. After 2 wk, subjects were switched to an isocaloric low-fat diet consisting of 15% fat, 65% carbohydrate, and 20% protein for another 2 wk. For the final 12 wk of the study, subjects consumed the same 15% fat diet ad libitum. At the end of each diet phase, CRP was measured by a high-sensitivity CRP assay. RESULTS: The weight of subjects remained stable during the first 4 wk of isocaloric diets. Plasma CRP concentrations after 2 wk on the weight-maintaining 35% fat diet and 2 wk on the isocaloric 15% fat diet were not significantly different (median +/- interquartile range 1.42 +/- 3.30 and 1.59 +/- 3.29 mg/L, respectively). Three months of ad libitum low-fat diet consumption resulted in a 4.1 +/- 0.7 kg weight loss associated with a decrease in CRP concentration to 1.17 +/- 2.03 mg/L (P = 0.03). CONCLUSION: Loss of body weight decreases CRP concentration, but a decrease in dietary fat without a concurrent change in body weight does not affect CRP concentration in overweight healthy subjects.

Adult↗
PubMed1997

Dietary fat and protein intake differ in modulation of prostate tumor growth, prolactin secretion and metabolism, and prostate gland prolactin binding capacity in rats.

The combined effects of dietary fat and protein concentration on prostate tumor growth and endocrine homeostasis were evaluated in male rats. A 2 x 2 factorial experiment examined the effects of protein (5 and 20% of energy as casein) and fat (10 and 40% of energy as corn oil) on the growth of the Dunning R3327-H transplantable prostate adenocarcinoma in Copenhagen x Fisher F1 rats. Rats fed protein-restricted diets for 20 wk exhibited lower energy intakes, final body weights and tumor growth rates. Weanling male Sprague-Dawley rats fed protein-restricted diets for 4 wk had serum concentrations of prolactin, growth hormone and testosterone which were 68, 17 and 85% of controls, respectively. After 16 wk of feeding, there were no effects of dietary protein on serum hormone concentrations despite reduced energy intake and body weight. The metabolic clearance rate of serum prolactin was lower in rats fed the low protein diets for 4 or 16 wk; however, no differences were noted when adjusted for body weight. In vivo studies employing intravenously injected 125I-labeled prolactin revealed slight alterations in the metabolism of circulating prolactin monomer or binding to serum proteins in protein-restricted rats. The maximal binding capacity of prolactin receptors on the prostate membrane fraction was 42% lower in rats fed diets restricted in protein despite normal serum hormone concentrations at 16 wk. Dietary fat had no effect on tumor growth or prolactin homeostasis although a slightly greater serum testosterone was noted in rats fed high fat diets. In contrast, restriction of dietary protein caused significant changes in energy intake, serum hormone concentrations, prolactin metabolism, prostatic prolactin binding capacity and prostate tumor growth rates. These studies support the hypothesis that dietary protein and energy intake, particularly during periods of rapid growth and development, may alter prostate biology and modulate the risk of future prostate cancer progression.

Adenocarcinoma↗
PubMed2000

Influence of dietary fat and vitamin E supplementation on free radical production and on lipid and protein oxidation in turkey muscle extracts.

The objectives of this study were to investigate the effects of dietary fat (6% soy oil or rapeseed oil or tallow) and alpha-tocopheryl acetate supplementation at two levels (30 or 200 ppm) on radical production, measured by ESR spectroscopy, and on lipid and protein oxidation in turkey muscle extracts oxidized by an enzymic system (NADPH, ADP, FeSO(4)/cytochrome P450 reductase). Two muscles were tested: pectoralis major (glycolytic) and sartorius (oxidative) muscles. Radical production measured by ESR was higher in pectoralis major muscle than in sartorius muscle, whereas lipid and protein oxidation was more important in sartorius muscle, showing the importance of the pro-/antioxidant ratio in oxidative processes in muscular cells and of the measurement methodology to appreciate the free radical production. Dietary fat had no effect on the level of ESR signals, whereas feeding of animals with soy oil induced higher oxidation of lipids. Protein oxidation was less sensitive to the nature of the dietary fat than lipid oxidation. Vitamin E supplementation significantly decreased radical production, as measured by ESR spectroscopy. Vitamin E also decreased lipid and protein oxidation, but the effect of vitamin E on protein oxidation was less pronounced than on lipid oxidation.

Animals↗
PubMed1996

Modulating effect of amount and types of dietary fat on colonic mucosal phospholipase A2, phosphatidylinositol-specific phospholipase C activities, and cyclooxygenase metabolite formation during different stages of colon tumor promotion in male F344 rats.

Epidemiological and laboratory animal model studies suggest that the effect of dietary fat in colon carcinogenesis depends not only on the amount but on its fatty acid composition. Animal model studies demonstrated that high dietary corn oil or safflower oil rich in omega-6 fatty acids increased the colon tumor promotion, whereas diets containing fish oil high in omega-3 fatty acids had no such enhancing effect. One of the mechanisms by which high dietary fat enhances colon carcinogenesis may be through the modulation of colonic mucosal phospholipase A2 (PLA2) and phosphatidylinositol-specific phospholipase C (PI-PLC), which are dominant pathways for arachidonic acid release and formation of eicosanoids. PI-PLC is also responsible for diacylglycerol formation and protein kinase C-dependent signal transduction and cell proliferation. In the present study, we investigated the modulating effect of high fat diets rich in omega-3 and omega-6 fatty acids on colonic mucosal PLA2, PI-PLC activities, and eicosanoid (prostaglandins and thromboxane B2) formation from arachidonic acid via cyclooxygenase (COX) during different stages of azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. At 5 weeks of age, groups of animals were fed the low-fat diet containing 5% corn oil. Beginning at 7 weeks of age, all animals except those intended for vehicle treatment received AOM s.c. once weekly for 2 weeks at a dose rate of 15 mg/kg body weight. Vehicle-treated groups received an equal volume of normal saline. One day after the second AOM or vehicle treatment, groups of animals were transferred to experimental diets containing 23.5% corn oil and 20.5% fish oil + 3% corn oil, whereas one group continued on the low-fat diet containing 5% corn oil. Groups of animals were then sacrificed at weeks 1, 12, and 36 after the second AOM-or saline-treatment. Colonic mucosa harvested at weeks 1, 12, and 36 and colonic tumors obtained at week 36 were analyzed for PLA2, PI-PLC, and eicosanoid formation from arachidonic acid by the action of COX. The results demonstrate that colon carcinogen treatment increases the activities of colonic mucosal PLA2 and PI-PLC and the formation of prostaglandins and thromboxane A2 from arachidonic acid through COX throughout the study period compared to saline-treated animals fed similar diets. The activities of PLA2, PI-PLC, and COX were significantly higher in colon tumors compared to colonic mucosa. These results also demonstrate that a high-fat diet containing corn oil increases colonic mucosal and tumor PLA2 and PI-PLC and the formation of prostaglandins and thromboxane B2 by the action of COX as compared to low dietary corn oil or a diet high in fish oil. The results of our study offer one of the mechanisms by which the amount and types of dietary fat modulate colon carcinogenesis.

Animals↗
PubMed1994

Dietary fat, sugar, and fiber predict body fat content.

OBJECTIVE: This study was conducted to determine the relationships among the specific components of dietary fat and carbohydrate and body fatness in lean and obese adults. DESIGN: Body composition determination was performed on each subject by hydrostatic weighing at residual volume. Subsequently, the individual components of dietary fat and carbohydrate were examined relative to body fatness using a 3-day food diary and a food frequency questionnaire. SUBJECTS: Subjects were 23 lean (11.1 +/- 2.9% body fat) men, 23 obese (29.2 +/- 3.8% body fat) men, 17 lean (16.7 +/- 3.3% body fat) women, and 15 obese (42.7 +/- 3.9% body fat) women who volunteered for free diet and body composition analyses. Inclusion criteria were 15% body fat for lean men, 25% for obese men, 20% for lean women, and 35% for obese women. STATISTICAL ANALYSIS PERFORMED: Group comparisons for dietary variables were made with a multivariate analysis of variance. RESULTS: No differences were found between lean and obese subjects for energy intake or total sugar intake, but obese subjects derived a greater portion of their energy from fat (33.1 +/- 2.6% and 36.3 +/- 2.3% for obese men and women, respectively, vs 29.1 +/- 1.3% and 29.6 +/- 2.0%, lean men and women, respectively). Percent of fat intake for saturated, monounsaturated, and polyunsaturated fats was not different among groups. Obese subjects derived a greater percentage of their sugar intake from added sugars than lean subjects (38.0 +/- 3.5% vs 25.2 +/- 2.0%, respectively, for men; 47.9 +/- 8.0% vs 31.4 +/- 3.4%, respectively, for women). Dietary fiber was lower for obese men (20.9 +/- 1.8 g) and women (15.7 +/- 1.1 g) than for lean men (27.0 +/- 1.8 g) and women (22.7 +/- 2.1 g). APPLICATIONS/CONCLUSIONS: Obesity is maintained primarily by a diet that is high in fat and added sugar and relatively low in fiber. Alterations in diet composition rather than energy intake may be a weight control strategy for overweight adults.

Adipose Tissue↗
PubMedDate not supplied

Dietary fat and risk of breast cancer according to hormone receptor status.

The association of dietary fat with breast cancer in prospective cohort studies has generally been weak and not statistically significant. However, these studies have not considered whether the risk related to fat intake may differ according to estrogen or progesterone receptor status. Dietary habits and other breast cancer risk factors were assessed by mailed questionnaire in January 1986 in 34,388 postmenopausal Iowa women. Through 1991, 724 incident breast cancer cases were ascertained in this cohort using the Iowa cancer registry. Joint estrogen and progesterone receptor status was determined for 479 (66%) breast cancers. For tumors that were positive for both estrogen and progesterone receptors (ER+/PR+) (n = 329), age- and energy-adjusted relative risks for breast cancer adjusted from lowest to highest third of fat intake were 1.0, 1.05, and 1.22 (P trend = 0.14). Corresponding risks for ER+/PR- tumors (n = 75) were 1.0, 0.85, and 1.05 (P trend = 0.86) and for ER-/PR- tumors (n = 61) were 1.0, 1.06, and 0.73 (P trend = 0.68). Only 14 cases were classified as having ER-/PR+ tumors. Adjustment for other breast cancer risk factors did not appreciably alter these findings. There was a suggestion that dietary fat may be associated with ER+/PR+ breast cancers and not other breast cancers. These results are also consistent with an interpretation of no association between dietary fat with breast cancer, regardless of hormone receptor status. It has been suggested that etiological studies of breast cancer should investigate associations according to receptor status. This study provides evidence of a subset of breast cancers that may be related to dietary factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed2000

Regulation of PPARgamma but not obese gene expression by dietary fat supplementation.

Leptin, the product of the obese gene, and peroxisome proliferator activated receptor gamma (PPARgamma) are important regulators of energy metabolism, adipogenesis, and immune function. In rodent models, both genes seem to respond at the mRNA and/or protein levels to dietary fat consumption. To determine the effect(s) of dietary saturated and polyunsaturated fatty acids on the expression (mRNA abundance) of these genes, adipose tissue was obtained from pigs fed three different dietary fat sources. Corn-soybean meal diets containing no added fat (NO, control) or 10% beef tallow (BT), safflower oil (SO), or fish oil (FO) were fed ad libitum (n = 12) for 12 weeks. The abundance of obese, PPARgamma1, and PPARgamma2 mRNA was quantified relative to 18S rRNA using ribonuclease protection assays. The gain:feed ratio was improved (P < 0.05) 21% by all fats with a corresponding reduction (P < 0.05) in feed intake. Relative to pigs fed NO, serum total cholesterol was increased (P < 0.01) in pigs fed BT and triglyceride and nonesterified fatty acid concentrations were increased (P < 0.01) by all supplemental fats. Serum insulin was increased (P < 0.10) only by SO. Neither obese nor PPARgamma1 mRNA abundance were responsive to added fat (P > 0.15). However, the abundance of PPARgamma2 mRNA was increased fourfold by SO compared with the NO diet. These data indicate that the abundance of obese mRNA is independent of dietary fat consumption per se, whether saturated or unsaturated, when feed consumption is reduced due to greater dietary caloric density. Furthermore, we provide evidence that expression of the PPARgamma2 gene in porcine adipose tissue is selectively responsive to SO (presumably linoleic acid, 18:2n-6).

Journal Article↗
PubMed1992

Insulin insensitivity is rapidly reversed in rats by reducing dietary fat from 40 to 30% of energy.

The objective of this study was to determine the effect of reducing dietary fat content from 40 to 30% of total energy on body composition and insulin sensitivity in rats. Female Sprague-Dawley rats were fed either a control diet (30% energy as fat) or a high fat diet (40% energy as fat) for 10 wk. In vivo glucose tolerance tests indicated that both basal and glucose-stimulated insulin concentrations were elevated in rats fed the high fat diet. Two groups of rats offered the high fat diet were then fed the control diet (HF,C) and two that had received the high fat diet were then fed a diet (30% energy as fat) containing a fat-mimetic carbohydrate (HF,M). Two groups continued to receive the high fat diet and two groups continued to receive the control diet. Rats were killed 1 and 2 wk after the diet switch. In vivo glucose tolerance tests indicated that insulin sensitivity was corrected in HF,C and HF,M rats after 3 d. Body fat content was greater in rats fed the high fat diet and remained high after 7 d of consuming either diet with 30% of energy from fat. There was no effect of diet on liver fatty acid utilization or on diaphragm glucose oxidation. Adipocytes from all treatment groups were insulin resistant, possibly due to feeding status or age of the rats. The results of this study suggest that a moderate reduction in fat intake, from 40 to 30% of energy, can produce a rapid improvement of insulin sensitivity in insulin-insensitive rats, independent of changes in body fat content and irrespective of the means used to reduce dietary fat content.

Adipose Tissue↗
PubMed1981

Dietary fat effects on blood insulin, glucose utilization, and milk protein content of lactating cows.

Relationships among dietary fat, glucose and insulin in blood plasma, and milk protein were investigated to determine mechanisms by which high fat diets depress milk protein percentage of lactating cows. Glucose clearance, determined by intravenous glucose infusion tolerance tests, of cows fed high fat diets was lower and insulin release higher than of control cows. Negative relationship between glucose utilization rate and insulin release was linear (correlation -.85), suggesting that fat feeding induced insulin resistance. Feeding lipid in a protected supplement did not change production of milk or milk protein but depressed milk protein percentage and increased quantity and concentration of milk fat. Concentrations of total lipids in blood plasma were increased whereas glucose and insulin were reduced by protected lipid supplement. Dietary fat may impair amino acid transport into the mammary gland and milk protein synthesis by inducing insulin resistance.

Animals↗
PubMed1984

Promotion of 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis by high dietary fat in the rat: possible role of intercellular communication.

The effect of high levels of dietary fat on the promotion phase of rat mammary tumorigenesis and the effect of unsaturated and saturated fatty acids on metabolic cooperation in hamster cells were examined. Female Sprague-Dawley rats were given iv injections of 5 mg 7,12-dimethylbenz[a]anthracene (DMBA) and subsequently placed on 20% high-fat (HF) and 4.5% corn oil control (CF) diets. Rats treated with DMBA and fed HF diet for the entire duration of the experiment developed more tumors with shorter latency than rats fed CF diet for the entire experiment. Rats fed HF diet for 3 weeks at different times after DMBA treatment showed similar, enhanced mammary tumor development. Lengthening the duration of HF diet treatment (0, 3, 6, 16 wk) increased mammary tumor development, suggesting a time dose-response relationship. Removal of the HF diet treatment partially reversed its stimulatory effects on tumor development. These results indicate that dietary fat acts as a classical tumor promoter to enhance mammary tumorigenesis. The influence of unsaturated and saturated fatty acids on metabolic cooperation between 6-thioguanine-sensitive (6-TGS) and 6-thioguanine-resistant (6-TGr) Chinese hamster V79 cells was examined. Linoleic acid, palmitoleic acid, and arachidonic acid significantly increased the recovery of 6-TGr cells at noncytotoxic concentrations. Stearic acid, palmitic acid, and arachadic acid had no effect on the recovery of 6-TGr cells at either cytotoxic or noncytotoxic concentrations. These results demonstrate that unsaturated fatty acids but not saturated fatty acids can inhibit metabolic cooperation between Chinese hamster V79 cells, and suggest, mechanistically, that high dietary levels of polyunsaturated fat could promote tumorigenesis by inhibition of intercellular communication.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Cholesterol metabolism in relation to aging and dietary fat in rats and humans.

A review of research in the authors' laboratories regarding effects of dietary fat polyunsaturation upon longevity in rats and some aspects of the regulation of cholesterol metabolism with regard to age of rats and humans is presented. The longevity of the rat was found to be enhanced by consumption of dietary fat providing a polyunsaturated to saturated fatty acid (P/S) ratio of 0.3 to 1, corresponding to about 5-12% of energy (en%) as linoleate, compared with less or more polyunsaturated fat. Mechanisms of the effects of the fats upon cholesterol metabolism were studied. With advancing age, there seems to be a decline in the rate of catabolism of cholesterol, resulting in longer retention in the body of the rat. In the human, there seems to be a decline in regulation of uptake of cholesterol by leukocytes and, therefore, perhaps other tissues, resulting in increased synthesis of cholesterol by the peripheral tissues. Moderate rather than high dietary consumption of polyunsaturated fat seems to be favorable to metabolic processes contributing to longevity.

Aging↗
PubMed1987

Influence of dietary fats on cell populations of line 168 mouse mammary tumors: a morphometric and ultrastructural study.

The effect of dietary fat concentration and saturation on cell composition and structure of line 168 mouse mammary tumors in vivo was studied using morphometry and electron microscopy. Both the concentration and saturation of fat fed to mice had a significant influence on the volume ratio of mast cells infiltrating line 168 tumors. Tumors of mice fed diets containing a high concentration (20%) of either safflower oil (SO) or palm oil (PO) had 2-3 times the volume ratio of mast cells than mice fed diets containing a low concentration (5%) of either fat. There were no significant differences among diets with respect to other inflammatory cell populations. Mice fed either one of the high fat diets had tumor cells with inclusions that ultrastructurally, appeared to consist of lipid. Dietary fat, however, had no observable affect on cell junctions or other morphological characteristics. Greater infiltration of mast cells in tumors of mice fed high fat diets and the eventual formation of new blood capillaries may explain the decreased latency of tumor onset and enhanced growth of tumors in mice fed diets with high concentrations of fat.

Animals↗
PubMed1998

Modulation of intestinal immune system by dietary fat intake: relevance to Crohn's disease.

Gut-associated lymphoid tissue is the major inductive site of the mucosal immune system, which is functionally independent of the systemic immune system. Both the amount and type of dietary fat modulate intestinal immune function. Absorption of long-chain fatty acids stimulates lymphocyte flux and lymphocyte blastogenesis in intestinal lymphatics. Long-chain fatty acid absorption also significantly enhances migration of T lymphocytes to Peyer's patches, possibly due to up-regulation of adhesion molecules, such as alpha4-integrin and L-selectin. Lipoproteins are involved in stimulation of lymphocyte function by both receptor-dependent and independent mechanisms. However, unsaturated fatty acids at higher concentrations have a suppressive effect on cell-mediated immunity via eicosanoid release, receptor affinity changes or interactions with intracellular signal transduction. Fat absorption also influences various other cells in the intestinal mucosa: increased cytokine release from intestinal epithelial cells follows long-chain fatty acid absorption. In Crohn's disease, elemental diets and total parenteral nutrition often induce remission, possibly by reducing antigenic load on activated immune cells in the intestine and, thus, down-regulating hyperreactive CD4 cells. Dietary oleic acid supplements caused an immunological reversal effect in the intestinal immune system of animals fed an elemental diet. An excess of long-chain fatty acids in an elemental diet, therefore, may negate its beneficial effect on gut-associated lymphoid tissues in Crohn's disease. In contrast, supplemental dietary fish oil apparently tends to prevent relapse of Crohn's disease. Because dietary fat intake is closely associated with immunological function of the intestinal mucosa, careful manipulation of dietary fat can be important in management of this disease.

Adjuvants, Immunologic↗
PubMed1992

Influence of dietary fat on the pharmacodynamics of propafenone in isolated, perfused rabbit hearts.

BACKGROUND: The fatty acid composition of the phospholipids in sarcolemma may significantly influence cell membrane functions. We evaluated the effects of dietary fat on the pharmacodynamics of the antiarrhythmic drug propafenone in isolated, perfused rabbit hearts. METHODS AND RESULTS: Three groups of weanling rabbits (n = 9 each group) were fed diets of 10% wt/wt lard, fish oil, or safflower oil for 40 days. Differences in electrophysiological variables were assessed at baseline and during propafenone perfusion. Myocardial concentration-effect relations were determined by plotting electrophysiological effects versus coronary sinus propafenone concentrations. The linoleic acid content of isolated sarcolemma was higher in the safflower group (33.4 +/- 11.4%) than in the lard (13.4 +/- 2.3%, p less than 0.01) and fish oil (8.5 +/- 1.4%, p less than 0.01) groups, whereas the omega-3 fatty acid content was higher in the fish oil group (p less than 0.01). During propafenone perfusion, greater changes in ventricular conduction time were observed in the lard group (22 +/- 11 msec) than in the safflower oil group (10 +/- 7 msec, p less than 0.05), whereas changes in ventricular conduction time in the fish oil group (16 +/- 7 msec) were intermediate between the lard and safflower oil groups. The slopes of the linear myocardial concentration-effect relations describing changes in QRS duration were steeper in the lard group (0.22 +/- 0.07 msec/micrograms/ml) than in the safflower oil group (0.13 +/- 0.04 msec/micrograms/ml, p less than 0.01) but not in the fish oil group (0.17 +/- 0.08 msec/microgram/ml, p = NS). Strength-interval curves were similar at baseline in all three groups. During propafenone perfusion, the threshold current was increased significantly at long coupling intervals (250-380 msec) in the lard group (1.8 +/- 1.0 mA) compared with the safflower oil group (0.8 +/- 0.6 mA, p less than 0.05) but not compared with the fish oil group (1.2 +/- 0.6 mA, p = NS). CONCLUSIONS: Dietary fat significantly alters the fatty acid composition of the phospholipids in sarcolemma. Propafenone effects on ventricular conduction time and ventricular excitability are significantly influenced by the type of dietary fat.

Animals↗
PubMed1995

Trafficking of dietary fat in lean rats.

Despite increasing interest in the role that fuel partitioning plays in determining body composition, the relative importance of oxidative versus storage pathways in the clearance of dietary fat remains unclear. A widely held view is that the primary destination of chylomicron triglyceride fatty acids (TGFA) is adipose tissue, and the primary source of lipid fuel for skeletal muscle is non-esterified fatty acids (NEFA). An alternate view is that muscle, not adipose tissue, is the primary site of TGFA clearance. This view is supported by estimates of the total lipoprotein lipase content of muscle and adipose tissue. To directly study the partitioning of dietary fat between oxidation and storage, 14C-labeled oleic acid was fed to Sprague Dawley rats and its metabolic rate followed over 30 days. Two hours after ingestion, more than 3.5 times as much label was found in skeletal muscle tissue (2.42 +/- 0.45 nmols) and CO2 (0.25 +/- 0.01 nmols) than was found in adipose tissue (0.71 +/- 0.14 nmols). Intramuscular triglyceride was the lipid class most extensively labeled. After skeletal muscle, liver was the next most important site of TGFA clearance. Surprisingly a substantial quantity of label remained associated with the GI tract even 24 hours after ingestion. Between 2 and 10 days following ingestion there was a net decline in the 14C content of muscle, liver and GI tract, associated with a net rise in the 14C content of adipose tissue. These findings demonstrate: 1) the importance of skeletal muscle and liver in whole organism TGFA clearance, 2) the importance of intramuscular partitioning of lipid fuels between direct oxidation and storage as TG, 3) the potentially important role of the GI tract in the delivery of dietary fat to the circulation 10-24 hours following ingestion, and 4) the stability of adipose tissue as a storage site. The complex nature of the tissue-specific clearance of TGFA over time is perhaps better described by the term "trafficking" than by the more commonly used term "partitioning." Future studies of TGFA clearance combined with sampling of relevant tissues over time will provide insight into the specific roles that abnormalities in liver, muscle and adipose tissue TGFA metabolism play in the development of hypertriglyceridemic disorders and states of increased or reduced body weight.

Adipose Tissue↗
PubMed2004

Sim1 gene dosage modulates the homeostatic feeding response to increased dietary fat in mice.

Haploinsufficiency of the transcription factor gene Sim1 has been previously implicated in hyperphagic obesity in humans and mice. To investigate the relation between Sim1 dosage and hyperphagia, we generated sim1-knockout mice and studied their growth and feeding behavior. Heterozygous mice weaned on standard chow consumed 14% more food per day than controls and developed obesity, hyperinsulinemia, and hyperleptinemia. The sim1 heterozygous mice were also significantly longer than controls. Heterozygous animals had modestly increased feeding efficiency, suggesting reduced energy expenditure, but voluntary wheel-running activity did not differ significantly between the two groups. We studied the effect of dietary fat on the feeding behavior of heterozygous sim1 mutant mice. The tempo and severity of weight gain were much greater in animals weaned on a high-fat diet. When acutely challenged with increased dietary fat, sim1 heterozygous mice weaned on the chow diet markedly increased their food consumption and caloric intake, whereas control mice reduced the mass of food they consumed and maintained approximately isocaloric intake. In wild-type adult mice, we detected Sim1 expression in the paraventricular and supraoptic nuclei, as previously reported in neonates, as well as in the amygdala and lateral hypothalamus, all regions implicated in feeding behavior. Our results indicate that Sim1 gene dosage modulates the homeostatic feeding response to increased dietary fat and likely plays a physiological role in the regulation of energy balance.

Aging↗