Metabolic and molecular action of <Emphasis Type="Italic">Trigonella foenum-graecum</Emphasis> (fenugreek) and trace metals in experimental diabetic tissues

Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycaemia resulting in defective insulin secretion, resistance to insulin action or both. The use of biguanides, sulphonylurea and other drugs are valuable in the treatment of diabetes mellitus; their use, however, is restricted by their limited action, pharmaco-kinetic properties, secondary failure rates and side effects. Trigonella foenum-graecum, commonly known as fenugreek, is a plant that has been extensively used as a source of antidiabetic compounds from its seeds and leaf extracts. Preliminary human trials and animal experiments suggest possible hypoglycaemic and anti-hyperlipedemic properties of fenugreek seed powder taken orally. Our results show that the action of fenugreek in lowering blood glucose levels is almost comparable to the effect of insulin. Combination with trace metal showed that vanadium had additive effects and manganese had additive effects with insulin on in vitro system in control and diabetic animals of young and old ages using adipose tissue. The Trigonella and vanadium effects were studied in a number of tissues including liver, kidney, brain peripheral nerve, heart, red blood cells and skeletal muscle. Addition of Trigonella to vanadium significantly removed the toxicity of vanadium when used to reduce blood glucose levels. Administration of the various combinations of the antidiabetic compounds to diabetic animals was found to reverse most of the diabetic effects studied at physiological, biochemical, histochemical and molecular levels. Results of the key enzymes of metabolic pathways have been summarized together with glucose transporter, Glut-4 and insulin levels. Our findings illustrate and elucidate the antidiabetic/insulin mimetic effects of Trigonella, manganese and vanadium.     

Medium‐Chain Oil Reduces Fat Mass and Down‐regulates Expression of Adipogenic Genes in Rats

Objective: To test the hypothesis that adipose tissue could be one of the primary targets through which medium‐chain fatty acids (MCFAs) exert their metabolic influence. Research Methods and Procedures: Sprague‐Dawley rats were fed a control high‐fat diet compared with an isocaloric diet rich in medium‐chain triglycerides (MCTs). We determined the effects of MCTs on body fat mass, plasma leptin and lipid levels, acyl chain composition of adipose triglycerides and phospholipids, adipose tissue lipoprotein lipase activity, and the expression of key adipogenic genes. Tissue triglyceride content was measured in heart and gastrocnemius muscle, and whole body insulin sensitivity and glucose tolerance were also measured. The effects of MCFAs on lipoprotein lipase activity and adipogenic gene expression were also assessed in vitro using cultured adipose tissue explants or 3T3‐L1 adipocytes. Results: MCT‐fed animals had smaller fat pads, and they contained a considerable amount of MCFAs in both triglycerides and phospholipids. A number of key adipogenic genes were down‐regulated, including peroxisome proliferator activated receptor γ and CCAAT/enhancer binding protein α and their downstream metabolic target genes. We also found reduced adipose tissue lipoprotein lipase activity and improved insulin sensitivity and glucose tolerance in MCT‐fed animals. Analogous effects of MCFAs on adipogenic genes were found in cultured rat adipose tissue explants and 3T3‐L1 adipocytes. Discussion: These results suggest that direct inhibitory effects of MCFAs on adiposity may play an important role in the regulation of body fat development.     

High sodium intake enhances insulin-stimulated glucose uptake in rat epididymal adipose tissue

Objective: This study investigated the effect of different sodium content diets on rat adipose tissue carbohydrate metabolism and insulin sensitivity. Methods and Procedures: Male Wistar rats were fed on normal‐ (0.5% Na⁺; NS), high‐ (3.12% Na⁺; HS), or low‐sodium (0.06% Na⁺; LS) diets for 3, 6, and 9 weeks after weaning. Blood pressure (BP) was measured using a computerized tail‐cuff system. An intravenous insulin tolerance test (ivITT) was performed in fasted animals. At the end of each period, rats were killed and blood samples were collected for glucose and insulin determinations. The white adipose tissue (WAT) from abdominal and inguinal subcutaneous (SC) and periepididymal (PE) depots were weighed and processed for adipocyte isolation and measurement of in vitro rates of insulin‐stimulated 2‐deoxy‐d ‐[³H]‐glucose uptake (2DGU) and conversion of ‐[U‐¹⁴C]‐glucose into ¹⁴CO₂. Results: After 6 weeks, HS diet significantly increased the BP, SC and PE WAT masses, PE adipocyte size, and plasma insulin concentration. The sodium dietary content did not influence the whole‐body insulin sensitivity. A higher half‐maximal effective insulin concentration (EC₅₀) from the dose‐response curve of 2DGU and an increase in the insulin‐stimulated glucose oxidation rate were observed in the isolated PE adipocytes from HS rats. Discussion: The chronic salt overload enhanced the adipocyte insulin sensitivity for glucose uptake and the insulin‐induced glucose metabolization, contributing to promote adipocyte hypertrophy and increase the mass of several adipose depots, particularly the PE fat pad.     

Lactate Production from Glucose and Response to Insulin in Perifused Adipocytes from Mesenteric and Epididymal Regions of Lean and Obese Rats

Lactate, an important metabolic substrate for peripheral tissues and the liver, is released in significant amounts from adipose tissue. Using a perifusion system, we measured lactate production from glucose and response to insulin in isolated mesenteric and epididymal adipocytes removed from fed or fasted male Wistar rats at two stages of growth and development: (a) lean rats (7 weeks to 9 weeks old, weighing ～250 g), and (b) fatter rats (6 months to 8 months old, weighing ～550 g). The results show that lactate production in perifused adipocytes is regulated by the prior nutritional state of the animals, by the adipose tissue region, and by the presence of insulin in the perifusate. In fat cells from lean rats, basal lactate production was significantly higher (p<0.05) in mesenteric cells when compared with epididymal cells, both in the fed state (7.8 nmol/10⁷ fat cells per minute vs. 2.9 nmol/10⁷ fat cells per minute) and after 2 days of fasting (13.6 nmol vs. 3.5 nmol). When the response to 1 mU/mL insulin was studied, however, the relative increase in lactate production produced by insulin was greater in the epididymal cells than in the mesenteric cells, in both the fed (194% vs. 91% over basal, respectively) and fasted (360% vs. 55% over basal, p<0.05) state. When larger epididymal adipocytes from fatter rats were compared with an equal number of smaller epididymal cells from leaner rats, the larger cells produced 4.99 nmol of lactate/10⁷ fat cells per minute, whereas the smaller cells produced 2.93 nmol (p=0.08). Large fat cells showed a small and nonsignificant response to insulin in either type of cell (epididymal vs. mesenteric) or nutritional state (fed vs. fasted). This study indicates that distinct regional differences exist in lactate production and response to insulin. Mesenteric adipose tissue, which drains directly into the portal vein and provides substrates to the liver, may be an important source of lactate for the hepatic processes of gluconeogenesis and glycogenesis.     

The modifying effect of manganese on the enzymic profiles and pathways of carbohydrate metabolism in rat liver and adipose tissue during development

The effect of Mn²⁺ on the pattern of emergence of enzymes in rat liver and adipose tissue was studied in weaned rats given a milk diet (high fat) or sucrose-casein diet (high carbohydrate) for three weeks. Addition of Mn²⁺ to the high fat diet was associated with induction of key glycolytic, lipogenic and pentose pathway enzymes in both liver and adipose tissue; parallel increases were found in the incorporation of [1-¹⁴C] glucose into lipid and CO₂. Mn²⁺ induced a change in the profile of enzyme activity similar in pattern to that found in rats given a high sucrose diet or that produced by insulin treatment. Mn²⁺ appears partially to overcome the regulatory feed-back mechanisms of the high fat diet and to provide a signal for the coordinated increase of glucose catabolic and lipogenic processes.     

Regulation and control of glucose overutilization in erythrocytes by vanadate

The insulin mimetic effect of vanadate inin vitro incubation of erythrocytes with high glucose concentrations showed an increase in sorbitol accumulation and glucose utilization using U-¹⁴C-glucose. Aldose reductase inhibitors and vanadate addition reversed the sorbitol accumulation, whereas insulin could not reverse it. Increased glucose utilization was also normalized with vanadium compounds. Increased activity of aldose reductase and sorbitol levels in diabetic animals were also normalized with vanadate treatment.     

The contribution of visceral fat to improved insulin signaling in Ames dwarf mice

Ames dwarf (Prop1^df, df/df) mice are characterized by growth hormone (GH), prolactin, and thyrotropin deficiency, remarkable extension of longevity and increased insulin sensitivity with low levels of fasting insulin and glucose. Plasma levels of anti‐inflammatory adiponectin are increased in df/df mice, while pro‐inflammatory IL‐6 is decreased in plasma and epididymal fat. This represents an important shift in the balance between pro‐ and anti‐inflammatory adipokines in adipose tissue, which was not exposed to GH signals during development or adult life. To determine the role of adipose tissue in the control of insulin signaling in these long‐living mutants, we examined the effects of surgical removal of visceral (epididymal and perinephric) adipose tissue. Comparison of the results obtained in df/df mice and their normal (N) siblings indicated different effects of visceral fat removal (VFR) on insulin sensitivity and glucose tolerance. The analysis of the expression of genes related to insulin signaling indicated that VFR improved insulin action in skeletal muscle in N mice. Interestingly, this surgical intervention did not improve insulin signaling in df/df mice skeletal muscle but caused suppression of the signal in subcutaneous fat. We conclude that altered profile of adipokines secreted by visceral fat of Ames dwarf mice may act as a key contributor to increased insulin sensitivity and extended longevity of these animals.     

Impairment of insulin signalling in peripheral tissue fails to extend murine lifespan

Impaired insulin/IGF1 signalling has been shown to extend lifespan in model organisms ranging from yeast to mammals. Here we sought to determine the effect of targeted disruption of the insulin receptor (IR) in non‐neuronal tissues of adult mice on the lifespan. We induced hemizygous (PerIRKO^+/?) or homozygous (PerIRKO^?/?) disruption of the IR in peripheral tissue of 15‐weeks‐old mice using a tamoxifen‐inducible Cre transgenic mouse with only peripheral tissue expression, and subsequently monitored glucose metabolism, insulin signalling and spontaneous death rates over 4 years. Complete peripheral IR disruption resulted in a diabetic phenotype with increased blood glucose and plasma insulin levels in young mice. Although blood glucose levels returned to normal, and fat mass was reduced in aged PerIRKO^?/? mice, their lifespan was reduced. By contrast, heterozygous disruption had no effect on lifespan. This was despite young male PerIRKO^+/? mice showing reduced fat mass and mild increase in hepatic insulin sensitivity. In conflict with findings in metazoans like Caenorhabditis elegans and Drosophila melanogaster, our results suggest that heterozygous impairment of the insulin signalling limited to peripheral tissues of adult mice fails to extend lifespan despite increased systemic insulin sensitivity, while homozygous impairment shortens lifespan.     

Insulin resistance is improved in high‐fat fed mice by photobiomodulation therapy at 630 nm

Photobiomodulation therapy (PBMT) in the infrared spectrum exerts positive effects on glucose metabolism, but the use of PBMT at the red spectrum has not been assessed. Male Swiss albino mice were divided into low‐fat control and high‐fat diet (HFD) for 12 weeks and were treated with red (630 nm) PBMT or no treatment (Sham) during weeks 9 to 12. PBMT was delivered at 31.19 J/cm², 60 J total dose per day for 20 days. In HFD‐fed mice, PBMT improved glucose tolerance, insulin resistance and fasting hyperinsulinemia. PBMT also reduced adiposity and inflammatory infiltrate in adipose tissue. Phosphorylation of Akt in epididymal adipose tissue and rectus femoralis muscle was improved by PBMT. In epididymal fat PBMT reversed the reduced phosphorylation of AS160 and the reduced Glut4 content. In addition, PBMT reversed the alterations caused by HFD in rectus femoralis muscle on proteins involved in mitochondrial dynamics and β‐oxidation. In conclusion, PBMT at red spectrum improved insulin resistance and glucose metabolism in HFD‐fed mice.      

Betaine Down Regulates Apelin Gene Expression in Cardiac and Adipose Tissues of Insulin Resistant Diabetic Rats Fed by High-Calorie Diet

Apelin is a newly discovered peptide that its serum level increases in diabetic patients with cardiovascular dysfunction. Recent studies indicate the beneficial actions of betaine in reducing the cardiovascular and metabolic complications, however data related to its effect on adipocytokine expression is limited. The aim of this study was to evaluate the effect of betaine supplementation on Apelin gene expression in cardiac muscle and adipose tissue of insulin resistance, diabetic rats fed by a high calorie diet. To induce insulin resistance rats were fed with high fat/high carbohydrate diet for five weeks and then 30 mg/kg STZ was injected intraperitoneally. After confirming of diabetes incidence (serum glucose above 7.5 mmol/l) the animals were treated with 1 % betaine in drinking water for 28 days. At days 14 and 28 after treatment, animals were euthanized and Apelin gene expression was evaluated by real time PCR and western blot in heart and adipose tissues. Serum levels of insulin, Apelin and glucose and HOMA–IR were also measured. Our results showed that feeding of rats by a high calorie diets caused insulin resistance, which was manifested by elevated plasma insulin, glucose and Apelin levels and also HOMA–IR. Apelin gene expression in heart and adipose tissues were significantly increased simultaneously with the progression of diabetes. Betaine supplementation decreased serum Apelin and down regulated Apelin expression in adipose tissue and cardiac muscle, particularly at day 28 of treatment. We concluded that betaine might improve metabolic and cardiovascular complications in diabetic patients by regulation of Apelin expression and secretion.     

Trans fat diet induces abdominal obesity and changes in insulin sensitivity in monkeys

Objective: There is conflicting evidence about the propensity of trans fatty acids (TFAs) to cause obesity and insulin resistance. The effect of moderately high intake of dietary monounsaturated TFAs on body composition and indices of glucose metabolism was evaluated to determine any pro‐diabetic effect in the absence of weight gain. Research Methods and Procedures: Male African green monkeys (Chlorocebus aethiops; n = 42) were assigned to diets containing either cis‐monounsaturated fatty acids or an equivalent diet containing the trans‐isomers (～8% of energy) for 6 years. Total calories were supplied to provide maintenance energy requirements and were intended to not promote weight gain. Longitudinal body weight and abdominal fat distribution by computed tomography scan analysis at 6 years of study are reported. Fasting plasma insulin, glucose, and fructosamine concentrations were measured. Postprandial insulin and glucose concentrations, and insulin‐stimulated serine/threonine protein kinase (Akt), insulin receptor activation, and tumor necrosis factor‐α concentrations in subcutaneous fat and muscle were measured in subsets of animals. Results: TFA‐fed monkeys gained significant weight with increased intra‐abdominal fat deposition. Impaired glucose disposal was implied by significant postprandial hyperinsulinemia, elevated fructosamine, and trends toward higher glucose concentrations. Significant reduction in muscle Akt phosphorylation from the TFA‐fed monkeys suggested a mechanism for these changes in carbohydrate metabolism. Discussion: Under controlled feeding conditions, long‐term TFA consumption was an independent factor in weight gain. TFAs enhanced intra‐abdominal deposition of fat, even in the absence of caloric excess, and were associated with insulin resistance, with evidence that there is impaired post‐insulin receptor binding signal transduction.     

Increased PC-1 phosphodiesterase activity and inhibition of glucose uptake in adipocytes of type 2 diabetic rats

This study was designed to understand the cellular mechanisms responsible for defects in the insulin-stimulated signal transduction pathway in a type 2 diabetic animal model. We examined the in vitro PC-1 phosphodiesterase activity and glucose uptake in adipose tissue of streptozotocin (STZ)-induced type 2 diabetic rats. The PC-1 activity was significantly increased in adipose tissue of diabetic rats (0.54 ± 0.08 nmol PNTP hydrolyzed/mg protein/min) compared with controls (0.29 ± 0.05 nmol PNTP hydrolyzed/mg protein/min, p < 0.05). Upon insulin stimulation (100 nM), glucose uptake in the adipose tissue of the controls (4.17 ± 1.28×10⁻⁸ μmol/mg/min) was significantly higher than that in the diabetic rats (1.26 ± 0.35×10⁻⁸; p < 0.05). These results suggest that elevated PC-1 phosphodiesterase activity and decreased glucose uptake in adipose tissues may be acquired characteristics contributing to the development of type 2 diabetes mellitus.     

Effect of insulin on lipolysis in adipose tissue of rats of different ages

Several authors have not been able to find any antilipolytic effect of insulin in adipose tissue "in vitro". We investigated the possible role of cell size and/or age of donors on this phenomenon. The lipolytic rates (glycerol release per cell) were lower in the small cells of the 4-6 weeks old rats than in the larger cells of the 25-30 weeks old animals; however, the difference disappeared when the data were expressed per unit of cell surface area. Insulin (0.5-50 ng/ml) failed to inhibit both maximally and submaximally noradrenaline stimulated lipolysis in the adipocytes of the young rats, but its antilipolytic action was fully restored by using glucose-free medium. Therefore, at our experimental conditions, a glucose dependent factor, possibly involving the preferential hydrolysis of newly synthetized triglycerides, seems to blunt or to mask the insulin induced inhibition of glycerol release. Relatively higher rates of glucose metabolism and a lower lipolysis in small fat cells might explain the difference in the action of insulin on glycerol release in the adipose tissue of young rats as compared to the older ones.     

Role of adiponectin and inflammation in insulin resistance of Mc3r and Mc4r knockout mice

Objective: To investigate the involvement of hypoadiponectinemia and inflammation in coupling obesity to insulin resistance in melanocortin‐3 receptor and melanocortin‐4 receptor knockout (KO) mice (Mc3/4rKO). Research Methods and Procedures: Sera and tissue were collected from 6‐month‐old Mc3rKO, Mc4rKO, and wild‐type C57BL6J litter mates maintained on low‐fat diet or exposed to high‐fat diet (HFD) for 1 or 3 months. Inflammation was assessed by both real‐time polymerase chain reaction analysis of macrophage‐specific gene expression and immunohistochemistry. Results: Mc4rKO exhibited hypoadiponectinemia, exacerbated by HFD and obesity, previously reported in murine models of obesity. Mc4r deficiency was also associated with high levels of macrophage infiltration of adipose tissue, again exacerbated by HFD. In contrast, Mc3rKO exhibited normal serum adiponectin levels, irrespective of diet or obesity, and a delayed inflammatory response to HFD relative to Mc4rKO. Discussion: Our findings suggest that severe insulin resistance of Mc4rKO fed a HFD, as reported in other models of obesity such as leptin‐deficient (Lep^ob/Lep^ob) and KK‐A^y mice, is linked to reduced serum adiponectin and high levels of inflammation in adipose tissue. Conversely, maintenance of normal serum adiponectin may be a factor in the relatively mild insulin‐resistant phenotype of severely obese Mc3rKO. Mc3rKO are, thus, a unique mouse model where obesity is not associated with reduced serum adiponectin levels. A delay in macrophage infiltration of adipose tissue of Mc3rKO during exposure to HFD may also be a factor contributing to the mild insulin resistance in this model.     

Long-term antidiabetic activity of vanadyl after treatment withdrawal: Restoration of insulin secretion?

In its vanadate (V⁵⁺) or vanadyl (V⁴⁺) forms, vanadium has been demonstrated to possess antidiabetic activity. Oral treatment of streptozotocin (STZ)-diabetic animals with either form is associated with correction of hyperglycemia, and prevention of diabetes-induced complications, although weight gain is unaffected. Vanadium treatment of non-diabetic animals lowers plasma insulin levels by reducing insulin demand, as these animals remain normoglycemic. These results suggest that vanadium hasin vivo insulin-mimetic or insulin-enhancing effects, in agreement with severalin vitro observations.Chronic treatment with vanadium has also been shown to result in sustained antidiabetic effects in STZ-diabetic animals long after treatment has ceased. Thus, at 13 weeks after withdrawal from treatment, corrected animals had normalized glucose and weight gain, and improved basal insulin levels. In addition, near-normal glucose tolerance was found despite an insignificant insulin response. Since vanadium accumulates in several tissue sites (e.g. bone, kidney) when pharmacological doses are administered, it is possible that stored vanadium may be important in maintaining near-normal glucose tolerance at least in the short-term following withdrawal from treatment. Recently, following withdrawal of vanadyl treatment up to 30 weeks, diabetic animals which had remained normoglycemic and had normalized glucose tolerance showed improvements in plasma insulin levels both in the basal state and in response to oral glucose, as compared to those which had reverted to hyperglycemia. The observed significant improvements in insulin capacity over the long-term (>3 months) suggests that a restored and/or preserved insulin secretion may be essential for maintained reversal of the diabetic state over a prolonged period after treatment is withdrawn.     

Metabolic Response to a Mixed Meal in Obese and Lean Women from Two South African Populations

Objective: Lower lipid and insulin levels are found during a glucose-tolerance test in obese black than obese white South African women. Therefore, β-cell function and lipid metabolism were compared in these populations during a mixed meal. Research Methods and Procedures: Blood concentrations of glucose, free fatty acids (FFAs), insulin, lipograms, and in vivo FFA oxidation were determined at fasting and for 7 hours after oral administration of a mixed emulsion containing glucose-casein-sucrose-lipid and [1-¹³C] palmitic acid in 8 lean black women (LBW), 10 obese black women (OBW), 9 lean white women (LWW), and 10 obese white women (OWW). Subcutaneous and visceral fat mass was assessed by computerized tomography. Results: Visceral fat area was higher in OWW (152.7 ± 17.0 cm²) than OBW (80.0 ± 6.7 cm²; p < 0.01). In OBW, 30-minute insulin levels were higher (604.3 ± 117.6 pM) than OWW (311.0 ± 42.9 pM; p < 0.05). Total triglyceride was higher in OWW (706.7 ± 96.0 mM × 7 hours) than OBW (465.7 ± 48.2 mM × 7 hours; p < 0.05) and correlated with visceral fat area (β = 0.38, p = 0.05). Palmitate oxidation was higher in lean than obese women in both ethnic groups and correlated negatively with fat mass (β = −0.58, p < 0.005). Discussion: The higher 30-minute insulin response in OBW may reflect a higher insulinotropic effect of FFAs or glucose. The elevated triglyceride level of OWW may be due to their higher visceral fat mass and possibly reduced clearance by adipose tissue.     

Serum Leptin Concentration and Insulin Sensitivity in Men with Abdominal Obesity

JOHANNSSON, GUDMUNDUR, CECILIA KARLSSON, LARS LÖNN, PER MÅRIN, PER BJÖRNTORP, LARS SJÖSTRÖM, BJÖRN CARLSSON, LENA M.S. CARLSSON, BENGT-ÅKE BENGTSSON. Serum leptin concentration and insulin sensitivity in men with abdominal obesity. Obes Res. 1998;6:416–421. Objective : We have examined the association between generalized adiposity, abdominal adiposity, insulin sensitivity, and serum levels of leptin in a cross-sectional study of abdominally obese men. Research Methods and Procedures : Thirty men, 48 to 66 years of age with a body mass index (BMI) of between 25 kg/m² and 35 kg/m² and a waist hip ratio of <0.95, were included in the study. Serum leptin concentration was measured using radioimmunoassay. Total body fat percentage was determined from total body potassium, abdominal adiposity was measured by computed tomography, and the glucose disposal rate (GDR) was measured during an euglycemic, hyperinsulinemic glucose clamp. Results : Significant correlations were found between serum leptin concentration and BMI, percentage body fat, abdominal subcutaneous adipose tissue, serum insulin, GDR, and 24-hour urinary-free Cortisol. In a multiple regression analysis, it was shown that abdominal subcutaneous adipose tissue, GDR, and BMI explained 72% of the variability of serum leptin concentration. GDR demonstrated an independent inverse correlation with serum leptin concentration. Discussion : In abdominally obese men with insulin resistance, it was demonstrated that most of the individual variability in serum leptin concentration was explained by the amount of subcutaneous abdominal adipose tissue, insulin sensitivity, and BMI.     

Self‐Selected Macronutrient Diet Affects Energy and Glucose Metabolism in Brown Fat‐Ablated Mice

Objective: Obese transgenic UCP‐DTA mice have largely ablated brown adipose tissue and develop obesity and diabetes, which are highly susceptible to a high‐fat diet. We investigated macronutrient self‐selection and its effect on development of obesity, diabetes, and energy homeostasis in UCP‐DTA mice. Research Methods and Procedures: UCP‐DTA and wild‐type littermates were fed a semisynthetic macronutrient choice diet (CD) ad libitum from weaning until 17 weeks. Energy homeostasis was assessed by measurement of food intake, food digestibility, body composition, and energy expenditure. Diabetes was assessed by blood glucose measurements and insulin tolerance test. Results: Wild‐type and UCP‐DTA mice showed a high fat preference and increased energy digestion on CD compared with a low‐fat standard diet. On CD, wild‐type mice accumulated less body fat (16.9%) than UCP‐DTA (32.6%) mice, although they had a higher overall energy intake. Compared with wild‐type mice, resting metabolic rate was reduced in UCP‐DTA mice irrespective of diet. UCP‐DTA mice progressively decreased their carbohydrate intake, resulting in an almost complete avoidance of carbohydrate. UCP‐DTA mice developed severe insulin resistance but showed decreased fed and fasted blood glucose on CD. Discussion: In contrast to wild‐type mice, UCP‐DTA mice were not able to reduce their weight gain efficiency on CD. This suggests that, because of the high fat preference of the background strain and the increased metabolic efficiency, brown adipose tissue‐deficient mice still develop obesity and insulin resistance on a macronutrient CD even when decreasing overall energy intake. Through the avoidance of carbohydrates, however, they are able to maintain normoglycemia.     

Enhanced utilization of glycerol for glyceride synthesis in isolated adipocytes from early pregnant rats

Adipose tissue normally has low glycerol kinase activity, but its expression is enhanced under conditions of augmented insulin sensitivity and/or obesity. Since these conditions occur during early pregnancy, the comparative utilization of glucose or glycerol by isolated adipocytes from rats at 0, 7, 14, or 20 days of pregnancy was studied. Incubations were carried out in the presence of [U¹⁴C]-glucose or -glycerol in medium supplemented or not with 5 mM glucose and 100 nM insulin. The conversion of glucose into esterified fatty acids and glyceride glycerol was greatest in adipocytes from 7-day pregnant rats, the effect being further enhanced by insulin. Both the amount of aquoporin 7 and the in vitro conversion of glycerol into glyceride glycerol were greatest in adipocytes of 7-day pregnant rats, the later being unaltered by insulin. In the presence of glucose, the overall glycerol utilization was lower than in its absence and glycerol conversion into glyceride glycerol was further decreased by insulin, the effect only being significant in adipocytes from 7-day pregnant rats. It is proposed that the enhanced utilization of glycerol for glyceride glycerol synthesis in adipose tissue contributes to the net accumulation of fat depots that normally takes place in early pregnancy.