Medium-chain triglycerides inhibit free radical formation and TNF-alpha production in rats given enteral ethanol

This study determined whether free radical formation by the liver, tumor necrosis factor (TNF)-alpha production by isolated Kupffer cells, and plasma endotoxin are affected by dietary saturated fat. Rats were fed enteral ethanol and corn oil (E-CO) or medium-chain triglycerides (E-MCT) and control rats received corn oil (C-CO) or medium-chain triglycerides (C-MCT) for 2 wk. E-CO rats developed moderate fatty infiltration and slight inflammation; however, E-MCT prevented liver injury. Serum aspartate aminotransferase levels, gut permeability, and plasma endotoxin doubled with E-CO but were blunted approximately 50% with E-MCT. In Kupffer cells from E-CO rats, intracellular calcium was elevated by lipopolysaccharide (LPS) in a dose-dependent manner. In cells from E-MCT rats, increases were blunted by approximately 40-50% at all concentrations of LPS. The LPS-induced increase in TNF-alpha production by Kupffer cells was dose dependent and was blunted by 40% by MCT. E-CO increased radical adducts and was reduced approximately 50% by MCT. MCT prevent early alcohol-induced liver injury, in part, by inhibition of free radical formation and TNF-alpha production by inhibition of endotoxin-mediated activation of Kupffer cells.     

Diphenyleneiodonium sulfate, an NADPH oxidase inhibitor, prevents early alcohol-induced liver injury in the rat

The oxidant source in alcohol-induced liver disease remains unclear. NADPH oxidase (mainly in liver Kupffer cells and infiltrating neutrophils) could be a potential free radical source. We aimed to determine if NADPH oxidase inhibitor diphenyleneiodonium sulfate (DPI) affects nuclear factor-kappaB (NF-kappaB) activation, liver tumor necrosis factor-alpha (TNF-alpha) mRNA expression, and early alcohol-induced liver injury in rats. Male Wistar rats were fed high-fat liquid diets with or without ethanol (10-16 g. kg(-1). day(-1)) continuously for up to 4 wk, using the Tsukamoto-French intragastric enteral feeding protocol. DPI or saline vehicle was administered by subcutaneous injection for 4 wk. Mean urine ethanol concentrations were similar between the ethanol- and ethanol plus DPI-treated groups. Enteral ethanol feeding caused severe fat accumulation, mild inflammation, and necrosis in the liver (pathology score, 4.3 +/- 0.3). In contrast, DPI significantly blunted these changes (pathology score, 0.8 +/- 0.4). Enteral ethanol administration for 4 wk also significantly increased free radical adduct formation, NF-kappaB activity, and TNF-alpha expression in the liver. DPI almost completely blunted these parameters. These results indicate that DPI prevents early alcohol-induced liver injury, most likely by inhibiting free radical formation via NADPH oxidase, thereby preventing NF-kappaB activation and TNF-alpha mRNA expression in the liver.     

Membrane lipids and ethanol tolerance in the mouse. The influence of dietary fatty acid composition

Mice of the TO Swiss strain received diets containing different amounts of saturated or unsaturated fat throughout life. These diets produced characteristic changes in cardiac phospholipid fatty acid composition, but produced no significant differences in fatty acid composition of phospholipids from a crude membrane fraction of brain. When littermates of these animals were exposed to ethanol vapour in an inhalation chamber it was observed that mice which had received a diet high in saturated fat lost the righting reflex at an estimated concentration of ethanol in blood higher than that required for mice receiving a control diet, or a diet rich in polyunsaturated fat. Analysis of the brain membrane fraction from those animals which had received ethanol revealed that mice receiving the highly saturated fat diet now had a significantly greater proportion of saturated fatty acids in brain membrane phospholipids. These results are discussed in relation to the hypothesis that brain membrane lipid composition may influence the behavioural response to ethanol.     

Effects of dietary saturated and polyunsaturated fat on lipoprotein lipase and hepatic triglyceride lipase activity

The effects of saturated and polyunsaturated dietary fat on the lipolytic activity of post-heparin plasma, lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) were studied in the rat. The lipolytic activity was studied from 0 to 60 min using labelled chylomicrons as the substrate. Triacylglycerol hydrolysis rate was higher for the plasma of rats fed high fat diets (14% fat by weight). Chylomicrons of rats fed saturated or unsaturated fats were hydrolyzed at the same rate within the first 15 min but afterwards hydrolysis of chylomicrons of rats fed saturated fat was slower. The activities of LPL and HTGL were increased by high fat diets. Unsaturated fat increased more LPL activity than saturated fat conversely, HTGL activity was enhanced more by saturated fat than by unsaturated fat.     

Manganese absorption and retention in rats is affected by the type of dietary fat

There is evidence that manganese (Mn) metabolism may be altered by the form and amount of dietary fat. Also, iron (Fe) absorption is greater with saturated fats, as compared to polyunsaturated fatty acids (PUFAs). The absorption of Fe and Mn are interrelated in many aspects; therefore, the form of dietary fat may indirectly alter Mn absorption. The reported studies were conducted to determine whether saturated fat, as compared to unsaturated fat, affected Mn absorption, retention, and metabolism. In experiment I, adult rats were fed diets containing either 0.7 or 100.4 μg/g Mn with the fat source as high-linoleic safflower oil or stearic acid. After 2 wk of equilibration, the animals were fed a test meal of ⁵⁴Mn followed by whole-body counting for 10 d. Manganese absorption was significantly (p<0.05) lower in the stearic acid group (0.9–4.8%) than in the safflower oil group (20–33.8%); however, the biological half-life was shorter in the safflower oil group. Retention of ⁵⁴Mn and total Mn was always significantly (p<0.05) greater in the safflower oil group when dietary Mn was low, but it was the same when dietary Mn was high. In experiment II, weanling rats were fed 1.3, 39.3, or 174.6 μg Mn/g and either stearate, high-oleic safflower oil or high-linoleic safflower oil for 8 wk. Long-term feeding of the stearate and low Mn-containing diet resulted in a significant (p<0.0001) reduction in heart superoxide dismutase activity and kidney and liver Mn concentrations compared to the other diets. These data show that stearic acid inhibitits Mn absorption, but it may not inhibit Mn retention when dietary Mn is high. The U.S. Department of Agriculture, Agricultural Research Service, Northern Plains Area, is an equal opportunity/affirmative action employer and all agency services are available without discrimination. Mention of a trademark or proprietary product does not constitute a guarantee or warranty of the product by the U.S. Department of Agriculture and does not imply its approval to the exclusion of other products that may also be suitable.     

Influence of dietary fatty acids composition, level of dietary fat and feeding period on some parameters of androgen metabolism in male rats

The aim of the present study was to determine the effect of the composition of dietary fatty acids, the duration of feeding period and dietary fat level on androgen metabolism in male rats. One hundred and twelve Wistar rats were divided into 18 groups which were fed three diets containing different types of fat (rapeseed [R], palm [P] and fish [F] oil) at either normal fat level (w/w; 5%) or high fat level (20%) during one, three or six weeks. Blood plasma level of androgen (testosterone+dihydrotestosterone) and testicular activity of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) were investigated. In addition, androgen content in cytosol of the heart, the target organ, was measured. Androgen concentration in both blood plasma and heart cytosol extracts was measured by radioimmunoassay. The activity of 17Beta-HSD was expressed as a conversion of [3H]androstendione to [3H]testosterone in soluble fraction of gonadal homogenates. Plasma androgen concentration was influenced by a type of dietary fat (p<0.05). The highest plasma level of androgen was observed in animals fed R diets rich in unsaturated fatty acids. Significantly lower androgen concentration was demonstrated in rats fed P diets rich in saturated fatty acids. Only the feeding period factor significantly influenced androgen content in cytosol fraction of heart muscle cells (p<0.01). A positive correlation was found between plasma androgen concentration in plasma and cytosol fraction of the heart muscle cells (r=0.63, p<0.001). The feeding period (p<0.001) and dietary fat type (p<0.05) significantly affected the activity of 17beta-HSD. The least 17beta-HSD activity was observed in animals consuming the P-20% diet for six weeks. In summary, dietary fat type and feeding period, but not fat level, significantly affected both testosterone production and testosterone uptake by the target organ in male rats. It was found that a rapeseed diet rich in unsaturated fatty acids stimulated the testicular function in rats.     

Dietary fat and immune function. I. Antibody responses, lymphocyte and accessory cell function in (NZB x NZW)F1 mice

The influence of dietary fat on autoimmunity in lupus-prone (NZB x NZW)F1 mice has been demonstrated. In defining further the effects of dietary lipid on the immune system of this strain, female weanling mice were placed on four diets differing in quantity and type of fat. Their immunologic response was then studied by a variety of tests at 4 and 7 mo of age. Few differences were seen among the four groups at 4 mo of age. At 7 mo of age, however, the mice receiving diets high in saturated and unsaturated fats had a reduced mitogenic response to T cell mitogens and an enhanced response to the B cell mitogen LPS. Immunoglobulin levels and delayed hypersensitivity responses did not show any consistent differences among the diet groups. At 7 mo, however, mice receiving diets high in unsaturated fat demonstrated hyperresponsiveness to injected sheep red blood cells as measured by the hemolytic plaque technique. In addition, peritoneal leukocytes from the same diet group exhibited an increased response to bromelain-treated autologous erythrocytes which was decreased after treatment with anti-Thy-1 antiserum and complement. Phagocytosis by peritoneal macrophages was significantly decreased in the animals fed high-fat diets, particular high saturated fat. Similarly, natural killer cell activity was markedly reduced in the mice with a high intake of saturated lipid, a finding which correlated with the in vitro production of interferon. These results indicate that diets high in fat influence immune responses and thus can affect the onset and severity of autoimmune disease. A low-fat diet can reduce the development of disease by maintaining normal immune responses. The data also suggest that unsaturated fat may influence T helper cell activity and therefore antibody production, whereas saturated fats may affect cellular immune responses which are dependent on membrane contact.     

Dietary fat and immune function. II. Effects on immune complex nephritis in (NZB x NZW)F1 mice

(NZB x NZW)F1 mice initiated on fat restriction at weanling were significantly protected from the development of immune complex glomerulonephritis. Whereas the mice on high-fat intake demonstrated immune depositions both in capillary walls and mesangial areas in a diffuse granular pattern, those on a low-fat diet with caloric content similar to the high-fat diets exhibited mesangial confinement of the depositions of immunoglobulins, complement, and retroviral gp70. In association with these divergent patterns of immune deposition, the mice on high-fat diets had evidence of extensive diffuse cellular proliferation, wire loop lesion, and sclerosis in the glomeruli. In contrast, most of the mice on the low-fat diet showed only mesangial cell and matrix proliferations. In addition, the group of mice fed high saturated fat showed more severe glomerular pathology as compared to those fed high unsaturated fat. Paradoxically, levels of circulating immune complexes (as measured by the polyethylene glycol precipitation technique) in the high saturated fat group were low and did not correlate with the findings by light and immunofluorescence microscopy. These findings suggest that dietary fat restriction can serve as either a prophylactic or effective therapeutic approach to murine lupus nephritis.     

Histopathological changes in rat pancreas and skeletal muscle associated with high fat diet induced insulin resistance

The effects of a high fat diet on the development of diabetes mellitus, insulin resistance and secretion have been widely investigated. We investigated the effects of a high fat diet on the pancreas and skeletal muscle of normal rats to explore diet-induced insulin resistance mechanisms. Forty-four male Wistar rats were divided into six groups: a control group fed standard chow, a group fed a 45% fat diet and a group fed a 60% fat diet for 3 weeks to measure acute effects; an additional three groups were fed the same diet regimens for 8 weeks to measure chronic effects. The morphological effects of the two high fat diets were examined by light microscopy. Insulin in pancreatic islets was detected using immunohistochemistry. The homeostasis model assessment of insulin resistance index and insulin staining intensity in islets increased significantly with acute administration of high fat diets, whereas staining intensity decreased with chronic administration of the 45% fat diet. Islet areas increased significantly with chronic administration. High fat diet administration led to islet degeneration, interlobular adipocyte accumulation and vacuolization in the pancreatic tissue, as well as degeneration and lipid droplet accumulation in the skeletal muscle tissue. Vacuolization in the pancreas and lipid droplets in skeletal muscle tissue increased significantly with chronic high fat diet administration. We suggest that the glucolipotoxic effects of high fat diet administration depend on the ratio of saturated to unsaturated fatty acid content in the diet and to the total fat content of the diet.     

Alcoholic liver disease in rats fed ethanol as part of oral or intragastric low-carbohydrate liquid diets

The intragastric administration of ethanol as part of a low-carbohydrate diet results in alcohol hepatotoxicity. We aimed to investigate whether comparable liver injury can be achieved by oral diet intake. Male Sprague-Dawley rats were fed ethanol as part of low-carbohydrate diets for 36-42 days either intragastrically or orally. Liver pathology, blood ethanol concentration, serum alanine amino transferase (ALT), endotoxin level, hepatic CYP2E1 induction, and cytokine profiles were assessed. Both oral and intragastric low-carbohydrate ethanol diets resulted in marked steatosis with additional inflammation and necrosis accompanied by significantly increased serum ALT, high levels of CYP2E1 expression, and production of auto-antibodies against malondialdehyde and hydroxyethyl free radical protein adducts. However, cytokine profiles differed substantially between the groups, with significantly lower mRNA expression of the anti-inflammatory cytokine interleukin 4 observed in rats fed low-carbohydrate diets orally. Inflammation and necrosis were significantly greater in rats receiving low-carbohydrate alcohol diets intragastrically than orally. This was associated with a significant increase in liver tumor necrosis factor alpha and interleukin 1beta gene expression in the intragastric model. Thus, oral low-carbohydrate diets produce more ethanol-induced liver pathology than oral high-carbohydrate diets, but hepatotoxicity is more severe when a low-carbohydrate diet plus ethanol is infused intragastrically and is accompanied by significant increases in levels of proinflammatory cytokines.     

The influence of dietary lipid supplementation on cardiac beta-adrenergic receptor adenylate cyclase activity in the marmoset monkey

Dietary lipid supplements high in either saturated fat derived from sheep kidney fat or unsaturated fat derived from sunflower seed oil, and a low mixed fat reference diet were fed to marmoset monkeys for 20 months and the effects on cardiac membrane lipid composition, and myocardial catecholamine-stimulated adenylate cyclase and beta-adrenergic receptor binding activity were investigated. For cardiac membranes enriched for beta-adrenergic binding activity, the dietary lipid treatment resulted in small changes in the proportion of saturated to unsaturated fatty acids and substantial changes in the (n - 6) to (n - 3) series of unsaturated fatty acids in the membrane phospholipids. The sheep kidney fat diet increased the cholesterol-to-phospholipid ratio in cardiac membranes in comparison to the other diets. This diet also significantly elevated basal and isoproterenol-, epinephrine- and norepinephrine-stimulated adenylate cyclase activity. The value of the dissociation constant (Kd) and the receptor number (Bmax) for the binding of [125I]ICYP to the beta-adrenergic receptor was significantly reduced in marmosets fed the sheep kidney fat diet. These results suggest that dietary lipids can influence the activity of the beta-adrenergic/adenylate cyclase system of the heart. Modulation of this transmembrane signalling system may be induced by changes in the properties of the associated membrane lipids, particularly by alteration in the membrane cholesterol-to-phospholipid ratio. This effect may be limited to those animal species in which the nature of the dietary fatty acid intake may be influencing cardiac membrane cholesterol homeostasis, which is in agreement with previous results in rats following dietary cholesterol supplementation (McMurchie et al. (1987) Biochim. Biophys. Acta 898, 137-153). ICYP, (-)-iodocyanopindolol.     

The interaction of dietary fatty acid and cholesterol on catecholamine-stimulated adenylate cyclase activity in the rat heart

Diets supplemented with high levels of saturated or unsaturated fatty acids supplied by addition of sheep kidney fat or sunflower seed oil, respectively, were fed to rats with or without dietary cholesterol. The effects of these diets on cardiac membrane lipid composition, catecholamine-stimulated adenylate cyclase and beta-adrenergic receptor activity associated with cardiac membranes, were determined. The fatty acid-supplemented diets, either with or without cholesterol, resulted in alterations in the proportion of the (n-6) to (n-3) series of unsaturated fatty acids, with the sunflower seed oil increasing and the sheep kidney fat decreasing this ratio, but did not by themselves significantly alter the ratio of saturated to unsaturated fatty acids. However, cholesterol supplementation resulted in a decrease in the proportion of saturated and polyunsaturated fatty acids and a dramatic increase in oleic acid in cardiac membrane phospholipids irrespective of the nature of the dietary fatty acid supplement. The cholesterol/phospholipid ratio of cardiac membrane lipids was also markedly increased with dietary cholesterol supplementation. Although relatively unaffected by the nature of the dietary fatty acid supplement, catecholamine-stimulated adenylate cyclase activity was significantly increased with dietary cholesterol supplementation and was positively correlated with the value of the membrane cholesterol/phospholipid ratio. Although the dissociation constant for the beta-adrenergic receptor, determined by [125I](-)-iodocyanopindolol binding, was unaffected by the nature of the dietary lipid supplement, the number of beta-adrenergic receptors was dramatically reduced by dietary cholesterol and negatively correlated with the value of the membrane cholesterol/phospholipid ratio. These results indicate that the activity of the membrane-associated beta-adrenergic/adenylate cyclase system of the heart can be influenced by dietary lipids particularly those altering the membrane cholesterol/phospholipid ratio and presumably membrane physico-chemical properties. In the face of these dietary-induced changes, a degree of homeostasis was apparent both with regard to membrane fatty acid composition in response to an altered membrane cholesterol/phospholipid ratio, and to down regulation of the beta-adrenergic receptor in response to enhanced catecholamine-stimulated adenylate cyclase activity.     

Effects of dietary fat types on body fatness,leptin, and ARC leptin receptor,NPY, and AgRP mRNA expression

Some, but not all, fats are obesogenic. The aim of the present studies was to investigate the effects of changing type and amount of dietary fats on energy balance, fat deposition, leptin, and leptin-related neural peptides: leptin receptor, neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC), in C57Bl/6J mice. One week of feeding with a highly saturated fat diet resulted in ~50 and 20% reduction in hypothalamic arcuate NPY and AgRP mRNA levels, respectively, compared with a low-fat or an n-3 or n-6 polyunsaturated high-fat (PUFA) diet without change in energy intake, fat mass, plasma leptin levels, and leptin receptor or POMC mRNA. Similar neuropeptide results were seen at 7 wk, but by then epididymal fat mass and plasma leptin levels were significantly elevated in the saturated fat group compared with low-fat controls. In contrast, fat and leptin levels were reduced in the n-3 PUFA group compared with all other groups. At 7 wk, changing the saturated fat group to n-3 PUFA for 4 wk completely reversed the hyperleptinemia and increased adiposity and neuropeptide changes induced by saturated fat. Changing to a low-fat diet was much less effective. In summary, a highly saturated fat diet induces obesity without hyperphagia. A regulatory reduction in NPY and AgRP mRNA levels is unable to effectively counteract this obesogenic drive. Equally high fat diets emphasizing PUFAs may even protect against obesity.     

Effects of dietary cholesterol and fat, sex and sire on lecithin-cholesterol acyltransferase activity in baboons

We analyzed the effects of dietary cholesterol, type of dietary fat, sex and sire progeny family on lecithin-cholesterol acyltransferase activity in 80 adult baboons. The animals were the progeny of 80 dams and 6 sires and were randomly assigned at birth to breast feeding or to one of three formulas containing 0.02, 0.30 or 0.60 mg cholesterol/ml. After weaning at 4 months of age the animals were fed one of four diets that were either high or low in cholesterol with 40% of the calories from either saturated or unsaturated fat. The fractional and molar rates of lecithin-cholesterol acyltransferase activity were measured at 7-8 years of age by an HPLC method. Infant diet (breast vs. formula feeding or level of cholesterol in formula had no effect on enzyme activity later in life. The adult diets that were high in cholesterol decreased the fractional lecithin-cholesterol acyltransferase rate by 20% / compared to diets low in cholesterol (7.89 vs. 9.84%/h, P less than 0.002), but dietary cholesterol did not affect the molar activity. Animals fed the high cholesterol diets had higher unesterified cholesterol concentrations compared to those fed the low cholesterol diets (38.1 mg/dl vs. 31.6 mg/dl, P less than 0.0001). The molar lecithin-cholesterol acyltransferase rate was increased 13% by saturated compared to unsaturated fat (83.3 vs. 73.6 nmol/h per ml plasma, P less than 0.07), but no effect of dietary fat was observed on the fractional enzyme activity. Females compared to males had significantly higher fractional (10.9 vs. 7.14%/h, P less than 0.0001) and molar lecithin-cholesterol acyltransferase activities (99.3 vs. 61.7 nmol/h per ml plasma, P less than 0.0001). After adjustment for the effects of diet and sex we observed differences in the fractional activity (range, 7.2-10.8%/h, P less than 0.04) and in the molar rate (range, 63.6-99.8 nmol/h per ml plasma, P less than 0.07) among the six sire progeny groups. The differences among sire progeny groups are evidence for genetic differences in lecithin-cholesterol acyltransferase activities among the baboon families.     

Green tea extract protects against early alcohol-induced liver injury in rats

Oxidants have been shown to be involved in alcohol-induced liver injury. This study was designed to test the hypothesis that the antioxidant polyphenolic extract of green tea, comprised predominantly of epigallocatechin gallate, protects against early alcohol-induced liver injury in rats. Male Wistar rats were fed high-fat liquid diets with or without ethanol (10-14 g kg(-1) day(-1)) and green tea (300 mg kg(-1) day(-1)) continuously for 4 weeks using an intragastric enteral feeding protocol. Mean body weight gains (approximately 4 g/day) were not significantly different between treatment groups, and green tea extract did not the affect average concentration or the cycling of urine ethanol concentrations (0-550 mg dl(-1) day(-1)). After 4 weeks, serum ALT levels were increased significantly about 4-fold over control values (35+/-3 IU/l) by enteral ethanol (114+/-18); inclusion of green tea extract in the diet significantly blunted this increase (65+/-10). Enteral ethanol also caused severe fatty accumulation, mild inflammation, and necrosis in the liver. While not affecting fat accumulation or inflammation, green tea extract significantly blunted increases in necrosis caused by ethanol. Furthermore, ethanol significantly increased the accumulation of protein adducts of 4-hydroxynonenal, a product of lipid peroxidation and an index of oxidative stress; green tea extract blocked this effect almost completely. TNFalpha protein levels were increased in liver by alcohol; this phenomenon was also blunted by green tea extract. These results indicate that simple dietary antioxidants, such as those found in green tea, prevent early alcohol-induced liver injury, most likely by preventing oxidative stress.     

Does enteral nutrition of dietary polyunsaturated fatty acids promote oxidative stress and tumour growth in ductal pancreatic cancer?: Experimental trial in Syrian Hamster

BACKGROUND: Type and composition of dietary fat intake is supposed to play an important role in carcinogenesis. Thus we investigated the effects of n-3, n-6 and n-9 polyunsaturated fatty acids (PUFA) on oxidative stress (lipidperoxidation) and tumour growth in ductal pancreatic cancer. METHODS: Ninety male hamsters were randomized into 6 groups (gr.) (n=15) and allocated to 3 main dietary categories: gr. 1 and 2 received a standard high fat diet (SHF, rich in n-6 PUFA), while gr. 3 and 4 were fed with a diet containing a mixture of n-3, n-6 and n-9 PUFA (SMOF) and gr. 5 and 6 had free access to a diet rich in n-3 PUFA (FISH-OIL). Gr. 1, 3 and 5 received weekly subcutaneous (s.c.) injections of 10 mg N-nitrosobis-2-oxypropylamine (BOP)/kg body weight in order to induce ductal pancreatic adenocarcinoma. Healthy control gr. 2, 4 and 6 were treated with 0.5 ml 0.9% sodium chloride s.c. After 32 weeks all animals were sacrificed. Removed pancreata were weighed and analysed histologically and biochemically. Activities of glutathionperoxidase (GSH-Px), superoxiddismutase (SOD) and levels of lipidperoxidation were measured in samples of pancreatic carcinoma as well as in tumour-free pancreatic tissue. RESULTS: While different diets did not significantly alter the overall incidence of histologically proven pancreatic adenocarcinoma, the number of macroscopically visible tumours was decreased in the FISH-OIL-gr. CONCLUSION: Different diets did not significantly influence the incidence of histologically proven pancreatic adenocarcinoma. However, administration of a diet rich in n-3 PUFA (FISH-OIL) resulted in a decrease of macroscopically visible tumours, thus indicating its beneficial effects in respect to attenuation of tumour growth.     

Glucagon-like peptide-1 regulation of carbohydrate intake is differentially affected by obesogenic diets

The incretin hormone glucagon‐like peptide‐1 (GLP‐1) has been implicated in the regulation of appetite by acting as an anorexigenic gut‐brain signal. The postprandial release of GLP‐1 can be blunted in obese humans and animals. However, it remains unknown whether obesogenic diets with varying fat and carbohydrate content may differentially influence the effectiveness of GLP‐1 feedback. To investigate this, male Sprague‐Dawley rats were fed a standard (low fat) chow diet, or one of two high‐energy diets varying in fat content (45 or 60 kcal%) for 28 weeks. Intake of sucrose and fructose solutions, two commonly added sugars in the Western diet, was then tested in nondeprived rats following administration of the GLP‐1 receptor agonist, Exendin‐4 (0, 0.5, 1, 2, 3 µg/kg; s.c.). Exendin‐4 dose‐dependently reduced short (2 h) sucrose and fructose intake. This effect was significantly attenuated in rats fed more dietary fat, despite both diets resulting in obesity. These findings demonstrate that intake of carbohydrates when offered as treats can be regulated by GLP‐1 and suggests that dietary fat consumption, rather than extra calories or obesity, may lead to impaired GLP‐1 feedback to curb carbohydrate intake. Future studies are warranted to investigate the relevance of these observations to humans and to elucidate the underlying mechanisms.     

Effect of ingestion of unsaturated fat on lipolytic activity of rat tissues

Homogenates of some rat tissues, incubated in Tris-maleate buffer containing bovine serum albumin, olive oil emulsion, heparin, and serum, liberated free fatty acids. The total lipolytic activity in tissues of rats fed a low fat, 20% lard, or 20% corn oil diet for 6 wk was measured. Similar activities were found in all the livers, but there was a significant increase in the total lipolytic activity of the mucosa, epididymal fat, and mesenteric tissues after ingestion of an unsaturated fat diet as compared with that containing a more saturated fat. From measurements of the lipolytic activity in the presence of 1 M NaCl or 0.2 M NaF and in the absence and presence of heparin and serum, the conclusion is drawn that more lipoprotein lipase was present in adipose tissue of rats on unsaturated fat diets. An increase in available lipoprotein lipase after unsaturated fat diets may aid in clearing lipids from the blood of these rats and thus in producing the lower blood lipid levels obtained.     

Tissue fatty acid composition of pigs fed different fat sources

Dietary fat influences the physico-chemical properties of meat, and fatty acid (FA) composition may have implications on human health. The objectives of the experiment were to study tissue FA partitioning and the effect of dietary fat source on tissue FA composition. Seventy crossbred gilts (61.8 ± 5.2 kg BW average) were fed one of seven treatments: a diet containing a very low level of fat (no fat (NF)) and six fat-supplemented diets (10%: tallow (T), high-oleic sunflower oil (HOSF), sunflower oil (SFO), linseed oil (LO), fat blend (FB: 55% tallow, 35% SFO, 10% LO) and fish oil blend (FO: 40% fish oil, 60% LO). Differential tissue FA depositions were observed, with flare fat being the most saturated, followed by intermuscular, and subcutaneous being the least saturated. Monounsaturated fatty acid (MUFA) deposition showed an opposite tissue pattern. Subcutaneous fat showed the highest MUFAs, intermuscular fat showed intermediate values and flare fat showed the lowest MUFAs. Intramuscular polyunsaturated fatty acid (PUFA) content was less susceptible to dietary treatment modifications compared with other depots. Significant tissue FA modifications were observed due to dietary treatments, mainly in diets rich in PUFA. The saturated fatty acids (SFA) were high in NF-fed and low in HOSF-fed animals, MUFA were high in HOSF-fed and low in SFO-, LO- and FO-fed animals, while PUFA were high in SFO- and LO-fed and low in HOSF-, T- and NF-fed animals. Pigs fed LO and FB showed detectable levels of EPA, which depended on the linolenic content of the diet. The only effective way to increase tissue DHA contents was to add DHA in the diet through FO feeding. Araquidonic acid was high in SFO diets and low in LO and FB diets, and also high in intramuscular fat compared with other tissues. EPA and DHA were also high in intramuscular fat compared with other fat depots. The deposition of oleic and linoleic acids depended on the composition of dietary fat, as their deposition varied between diets, even at similar levels of intake of each FA. The NF diet resulted in the greatest proportion of SFAs (palmitic and stearic) of all treatments tested. SFAs were less susceptible to modification than MUFA in response to the different PUFA levels supplemented in the diet. T resulted in less fat deposition in some of the fat depots and more in others, suggesting that T could partition fat differently among fat depots.     

Globular adiponectin resistance develops independently of impaired insulin-stimulated glucose transport in soleus muscle from high-fat-fed rats

High-fat (HF) diets induce insulin resistance and alter lipid metabolism, although controversy exists regarding the impact of saturated vs. polyunsaturated fats. Adiponectin (Ad) stimulates fatty acid (FA) oxidation and improves insulin sensitivity in humans and rodents, due in part to the activation of AMP-activated protein kinase (AMPK) and subsequent deactivation of acetyl coenzyme A carboxylase (ACC). In genetically obese, diabetic mice, this acute stimulatory effect on AMPK in muscle is lost. The ability of a HF diet to induce skeletal muscle Ad resistance has not been examined. The purpose of this study was to determine whether Ad's effects on FA oxidation and AMPK/ACC would be reduced following different HF diets, and if this coincided with the development of impaired maximal insulin-stimulated glucose transport. Rats were fed a control (10% kcal fat, CON), high unsaturated fat (60% kcal safflower oil, SAFF), or high saturated fat diet (60% kcal lard, LARD) for 4 wk. Following the dietary intervention, glucose transport, lipid metabolism, and AMPK/ACC phosphorylation were measured in the presence and absence of globular Ad (gAd, 2.5 microg/ml) in isolated soleus muscle. LARD rats showed reduced rates of maximal insulin-stimulated glucose transport compared with CON and SAFF (+68 vs. +172 and +184%, P < or = 0.001). gAd increased pACC (+25%, P < or = 0.01) and FA oxidation (+28%, P < or = 0.05) in CON rats, but not in either HF group. Thus 4 wk of HF feeding results in the loss of gAd stimulatory effect on ACC phosphorylation and muscle FA oxidation, and this can occur independently of impaired maximal insulin-stimulated glucose transport.