Glucose Metabolism In Adipose Tissue Research Articles

Greater molecular potential for glucose metabolism in adipose tissue and skeletal muscle of women compared with men.

Women typically have less muscle mass and more fat mass than men, while at the same time possessing similar or even greater whole-body insulin sensitivity. Our study aimed to investigate the molecular factors in primarily adipose tissue, but also in skeletal muscle, contributing to this sex difference. In healthy, moderately active premenopausal women and men with normal weight (28 ± 5 and 23 ± 3 years old; BMI 22.2 ± 1.9 and 23.7 ± 1.7) and in healthy, recreationally active women and men with overweight (32.2 ± 6 and 31.0 ± 5 years old; BMI 29.8 ± 4.3 & 30.9 ± 3.7) matched at age, BMI, and fitness level, we assessed insulin sensitivity and glucose tolerance with a hyperinsulinemic-euglycemic clamp or oral glucose tolerance test and studied subcutaneous adipose tissue and skeletal muscle samples with western blotting. Additionally, we traced glucose-stimulated glucose disposal in adipose tissues of female and male C57BL/6J littermate mice aged 16 weeks and measured glucose metabolic proteins. Our findings revealed greater protein expression related to glucose disposal in the subcutaneous adipose tissue (AKT2, insulin receptor, glucose transport 4) and skeletal muscle (hexokinase II, pyruvate dehydrogenase) in women compared to matched men with normal weight and with overweight. This increased protein capacity for glucose uptake extended to white adipose tissues of mice accompanied with ~2-fold greater glucose uptake compared to male mice. Furthermore, even in the obese state, women displayed better glucose tolerance than matched men, despite having 46% body fat and 20 kg less lean mass. In conclusion, our findings suggest that the superior potential for glucose disposal in female subcutaneous adipose tissue and skeletal muscle, driven by greater expression of various glucose metabolic proteins, compensates for their lower muscle mass. This likely explains women's superior glucose tolerance and tissue insulin sensitivity compared to men.

Electrochemiluminescent evaluation of GLUT4 expression in rat adipocytes induced by Ganoderma lucidum polysaccharides

Glucose transporter 4 (GLUT4) directly facilitates cellular uptake of glucose and plays a crucial role in mammalian adipose tissue glucose metabolism. In this work, we constructed a cytosensor for sensitive electrochemiluminescence (ECL) detection of GLUT4 in rat adipocytes (RA cells). A carbon nanotube sponge (CNTSP) was selected to fabricate a permeable electrode to overcome the steric hindrance of cells on the electrode. The expression of GLUT4 after treatment with Ganoderma lucidum polysaccharide (GLP) was assessed by analyzing the luminescence emitted from cell-surface ECL probes. Our preliminary results suggest that GLP promote the expression of GLUT4, thereby enhancing the uptake of the fluorescent glucose 2-NBDG. Treatment with GLP affected GLUT4 expression in RA cells in a dose-dependent manner. Additionally, the ECL cytosensor contributes to the development of ECL imaging of receptors on the cell surface for clinical drug evaluation.

Arsenic and adipose tissue: an unexplored pathway for toxicity and metabolic dysfunction.

Arsenic-contaminated drinking water can induce various disorders by disrupting lipid and glucose metabolism in adipose tissue, leading to insulin resistance. It inhibits adipocyte development and exacerbates insulin resistance, though the precise impact on lipid synthesis and lipolysis remains unclear. This review aims to explore the processes and pathways involved in adipogenesis and lipolysis within adipose tissue concerning arsenic-induced diabetes. Although arsenic exposure is linked to type 2 diabetes, the specific role of adipose tissue in its pathogenesis remains uncertain. The review delves into arsenic's effects on adipose tissue and related signaling pathways, such as SIRT3-FOXO3a, Ras-MAP-AP-1, PI(3)-K-Akt, endoplasmic reticulum stress proteins, CHOP10, and GPCR pathways, emphasizing the role of adipokines. This analysis relies on existing literature, striving to offer a comprehensive understanding of different adipokine categories contributing to arsenic-induced diabetes. The findings reveal that arsenic detrimentally impacts white adipose tissue (WAT) by reducing adipogenesis and promoting lipolysis. Epidemiological studies have hinted at a potential link between arsenic exposure and obesity development, with limited research suggesting a connection to lipodystrophy. Further investigations are needed to elucidate the mechanistic association between arsenic exposure and impaired adipose tissue function, ultimately leading to insulin resistance.

DHA promotes healthy adipose tissue remodeling and carbohydrate utilization in grass carp (Ctenopharyngodon idellus) and largemouth bass (Micropterus salmoides)

Due to the wide usage of high-carbohydrate diets in aquaculture, improving the ability of fish to utilize high-carbohydrate diets is one of the important issues in aquaculture. Adipose tissue is an essential organ for storing energy and plays a vital role in glucose homeostasis. In this study, RNA sequencing reveals that docosahexaenoic acid (DHA) promoted the expression of the glucose metabolism related-genes in grass carp adipocytes, raising the hypothesis that DHA may attenuate the adverse effect of high-carbohydrate diets on fish via promoting glucose metabolism in adipose tissue. To verify this hypothesis, a total of 180 juvenile grass carp (14.24 ± 0.43 g) and a total of 180 largemouth bass (40.03 ± 0.12 g) were randomly distributed into 18 tanks (200 L), respectively, and fed with high-carbohydrate diets containing DHA. The results showed that high-carbohydrate diets promoted glycolysis and inhibited lipolysis and fatty acid β-oxidation, leading to the excessive accumulation of abdominal fat and adipose tissue inflammation. After feeding high-carbohydrate diets supplementation with DHA, glucose transporter type 4 (GLUT4) mediated-glucose uptake was increased in adipose tissue, resulting in significantly decreased blood glucose in grass carp and largemouth bass (P < 0.05). And then, the glucose was converted to triglyceride through the glucose-6-phosphate dehydrogenase (G6PD) mediated-pentose phosphate pathway, de novo synthesis of fatty acids and triglyceride (TG) synthesis. Subsequently, the resulting TG was broken down through lipolysis and fatty acid β-oxidation. These reprogrammed metabolic processes inhibited the excessive accumulation of abdominal fat. In addition, DHA attenuated inflammation in adipose tissue, and further reduced the levels of inflammatory cytokines in serum (P < 0.05), indicating that DHA promotes healthy adipose tissue remodeling. Ultimately, these benefits improved the growth performance of grass carp and largemouth bass fed with high-carbohydrate diets. Taken together, our study indicates that adipose tissue is an important target for improving the negative effects of high-carbohydrate diets, and DHA could promote healthy adipose tissue remodeling and improve carbohydrate utilization in fish by reprogramming the glucose and lipid metabolism in adipose tissues.

Host Metabolic Changes during Mycobacterium Tuberculosis Infection Cause Insulin Resistance in Adult Mice.

Tuberculosis (TB) is a highly infectious bacterial disease that primarily attacks the lungs. TB is manifested either as latent TB infection (LTBI) or active TB disease, the latter posing a greater threat to life. The risk of developing active TB disease from LTBI is three times higher in individuals with type 2 diabetes mellitus (T2DM). The association between TB and T2DM is becoming more prominent as T2DM is rapidly increasing in settings where TB is endemic. T2DM is a chronic metabolic disorder characterized by elevated blood glucose, insulin resistance, and relative insulin deficiency. Insulin resistance and stress-induced hyperglycemia have been shown to be increased by TB and to return to normal upon treatment. Previously, we demonstrated that adipocytes (or fat tissue) regulate pulmonary pathology, inflammation, and Mycobacterium tuberculosis (Mtb) load in a murine model of TB. Metabolic disturbances of adipose tissue and/or adipocyte dysfunction contribute to the pathogenesis of T2DM. Thus, pathological adipocytes not only regulate pulmonary pathology, but also increase the risk for T2DM during TB infection. However, the cellular and molecular mechanisms driving the interaction between hyperglycemia, T2DM and TB remain poorly understood. Here, we report the impact of Mtb infection on the development of insulin resistance in mice fed on a regular diet (RD) versus high-fat diet (HFD) and, conversely, the effect of hyperglycemia on pulmonary pathogenesis in juvenile and adult mouse models. Overall, our study demonstrated that Mtb persists in adipose tissue and that Mtb infection induces irregular adipocyte lipolysis and loss of fat cells via different pathways in RD- and HFD-fed mice. In RD-fed mice, the levels of TNFα and HSL (hormone sensitive lipase) play an important role whereas in HFD-fed mice, ATGL (adipose triglyceride lipase) plays a major role in regulating adipocyte lipolysis and apoptosis during Mtb infection in adult mice. We also showed that Mtb infected adult mice that were fed an RD developed insulin resistance similar to infected adult mice that were overweight due to a HFD diet. Importantly, we found that a consequence of Mtb infection was increased lipid accumulation in the lungs, which altered cellular energy metabolism by inhibiting major energy signaling pathways such as insulin, AMPK and mToR. Thus, an altered balance between lipid metabolism and glucose metabolism in adipose tissue and other organs including the lungs may be an important component of the link between Mtb infection and subsequent metabolic syndrome.

Evidence of a Gastro-Duodenal Effect on Adipose Tissue and Brain Metabolism, Potentially Mediated by Gut-Liver Inflammation: A Study with Positron Emission Tomography and Oral 18FDG in Mice.

Interventions affecting gastrointestinal (GI) physiology suggest that the GI tract plays an important role in modulating the uptake of ingested glucose by body tissues. We aimed at validating the use of positron emission tomography (PET) with oral 18FDG administration in mice, and to examine GI effects on glucose metabolism in adipose tissues, brain, heart, muscle, and liver, and interfering actions of oral lipid co-administration. We performed sequential whole-body PET studies in 3 groups of 10 mice, receiving i.p. glucose and 18FDG or oral glucose and 18FDG ± lipids, to measure tissue glucose uptake (GU) and GI transit, and compute the absorption lumped constant (LCa) as ratio of oral 18FDG-to-glucose incremental blood levels. GI and liver histology and circulating hormones were tested to generate explanatory hypothesis. Median LCa was 1.18, constant over time and not significantly affected by lipid co-ingestion. Compared to the i.p. route, the oral route (GI effect) resulted in lower GU rates in adipose tissues and brain, and a greater steatohepatitis score (+17%, p = 0.03). Lipid co-administration accelerated GI transit, in relation to the suppression in GIP, GLP1, glucagon, PP, and PYY (GI motility regulators), abolishing GI effects on subcutaneous fat GU. Duodenal crypt size, gastric wall 18FDG uptake, and macro-vesicular steatosis were inversely related to adipose tissue GU, and positively associated with liver GU. We conclude that 18FDG-PET is a suitable tool to examine the role of the GI tract on glucose transit, absorption, and bio-distribution. The GI effect consists in the suppression of glucose metabolism selectively in organs responsible for energy intake and storage, and is blunted by lipid ingestion. Modulation of gut and liver inflammation, as reflected by high GU, may be involved in the acute signalling of the energy status.

Role of Estrogen and Its Receptors in Adipose Tissue Glucose Metabolism in Pre- and Postmenopausal Women

ContextReduced estrogen levels in postmenopausal women predispose them to metabolic side effects, including insulin resistance and type 2 diabetes; however, the cellular mechanisms are not well understood.ObjectiveThis work aimed to study the expression of estrogen receptors in adipose tissue from pre- and postmenopausal women and the effects of estradiol (E2) on glucose uptake of adipocytes.MethodsSubcutaneous (SAT) and visceral adipose tissue (VAT) obtained from pre- and postmenopausal women (19-51 and 46-75 years old, respectively) were used to measure gene expression of ESR1 and ESR2. SAT tissue was incubated with E2, and glucose uptake and estrogen receptor levels were measured. Polymorphisms in ESR1 and ESR2 were addressed in public databases to identify single nucleotide polymorphisms associated with metabolic traits.Results ESR2 expression was lower in pre- vs postmenopausal women, corresponding to lower ESR1:ESR2 gene expression ratio in postmenopausal women. In premenopausal women, the expression of ESR1 was higher in VAT than in SAT. In both pre- and postmenopausal women, ESR2 expression was lower in VAT than in SAT. In late, but not pre- or early postmenopausal women, E2 reduced glucose uptake and GLUT4 protein and increased expression of ESR2. ESR1 polymorphisms were associated with weight, body fat distribution, and total cholesterol, and ESR2 polymorphisms were associated with total cholesterol and triglyceride levels and with body fat percentage.ConclusionE2 inhibits glucose utilization in human adipocytes in late postmenopausal women. Changes in glucose utilization over time since menopause may be explained by a lower ESR1:ESR2 ratio. This can have clinical implications on the timing of estrogen treatment in postmenopausal women.

Role of the ACE2/Ang-(1-7)/Mas axis in glucose metabolism.

The renin-angiotensin system (RAS) helps to regulate cardiovascular function, the maintenance of electrolyte and fluid balance, and blood pressure. The RAS contains two axes; the angiotensin-converting enzyme/angiotensin II/Ang II type 1 receptors (ACE/Ang II/AT1) classic axis, which has a role in regulating blood pressure, vascular oxidative stress, coagulation, and cellular proliferation. The other is the angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas receptors (ACE2/Ang-(1-7)/Mas) axis, which can inhibit the former axis, improve fat metabolism, reduce inflammation and oxidative stress, and enhance glucose tolerance and insulin sensitivity. The ACE2/Ang-(1-7)/Mas axis is found in blood vessels, kidneys, liver, pancreas and the brain. It can protect the body from abnormalities in glucose metabolism. The ACE2/Ang-(1-7)/Mas axis can enhance glucose tolerance and improve insulin sensitivity by protecting pancreatic β cells, increasing insulin secretion, improving glucose metabolism in adipose tissue, enhancing glucose uptake by skeletal muscle, and inhibiting hepatic gluconeogenesis. This article reviews the main characteristics and functions of the ACE2/Ang-(1-7)/Mas axis and its regulation of glucose metabolism in order to demonstrate its potential as a target for the treatment of metabolic diseases such as diabetes.

TIR-Domain-Containing Adaptor-Inducing Interferon-β (TRIF) Is Involved in Glucose Metabolism in Adipose Tissue through the Insulin/AKT Signaling Pathway.

Obesity significantly increases the risk of developing type 2 diabetes mellitus and other metabolic diseases. Obesity is associated with chronic low-grade inflammation in white adipose tissues, which is thought to play an essential role in developing insulin resistance. Many lines of evidence indicate that toll-like receptors (TLRs) and their downstream signaling pathways are involved in development of chronic low-grade inflammation and insulin resistance, which are associated with obesity. Mice lacking molecules positively involved in the TLR signaling pathways are generally protected from high-fat diet-induced inflammation and insulin resistance. In this study, we have determined the effects of genetic deficiency of toll/interleukin-1 receptor-domain-containing adaptor-inducing interferon-β (TRIF) on food intake, bodyweight, glucose metabolism, adipose tissue macrophage polarization, and insulin signaling in normal chow diet-fed mice to investigate the role of the TRIF-dependent TLR signaling in adipose tissue metabolism and inflammation. TRIF deficiency (TRIF−/−) increased food intake and bodyweight. The significant increase in bodyweight in TRIF−/− mice was discernible as early as 24 weeks of age and sustained thereafter. TRIF−/− mice showed impaired glucose tolerance in glucose tolerance tests, but their insulin tolerance tests were similar to those in TRIF+/+ mice. Although no difference was found in the epididymal adipose mass between the two groups, the percentage of CD206+ M2 macrophages in epididymal adipose tissue decreased in TRIF−/− mice compared with those in TRIF+/+ mice. Furthermore, activation of epididymal adipose AKT in response to insulin stimulation was remarkably diminished in TRIF−/− mice compared with TRIF+/+ mice. Our results indicate that the TRIF-dependent TLR signaling contributes to maintaining insulin/AKT signaling and M2 macrophages in epididymal adipose tissue under a normal chow diet and provide new evidence that TLR4-targeted therapies for type 2 diabetes require caution.

LRRK2 Inhibition Ameliorates Dexamethasone-Induced Glucose Intolerance via Prevents Impairment in GLUT4 Membrane Translocation in Adipocytes.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are associated with Parkinson's disease. LRRK2 is a large protein with multiple functional domains, including a guanosine 5'-triphosphate (GTP)-binding domain and a protein kinase domain. Recent studies indicated that the members of the Rab GTPase family, Rab8a and Rab10, which are involved in the membrane transport of the glucose transporter type 4 (GLUT4) during insulin-dependent glucose uptake, are phosphorylated by LRRK2. However, the physiological role of LRRK2 in the regulation of glucose metabolism is largely unknown. In the present study, we investigated the role of LRRK2 using dexamethasone (DEX)-induced glucose intolerance in mice. LRRK2 knockout (KO) mice exhibited suppressed glucose intolerance, even after treatment with DEX. The phosphorylation of LRRK2, Rab8a and Rab10 was increased in the adipose tissues of DEX-treated wild-type mice. In addition, inhibition of the LRRK2 kinase activity prevented the DEX-induced inhibition of GLUT4 membrane translocation and glucose uptake in cultured 3T3-L1 adipocytes. These results suggest that LRRK2 plays an important role in glucose metabolism in adipose tissues.

A FACS-based approach to obtain viable eosinophils from human adipose tissue

Eosinophils have been widely investigated in asthma and allergic diseases. More recently, new insights into the biology of these cells has illustrated eosinophils contribute to homeostatic functions in health such as regulation of adipose tissue glucose metabolism. Human translational studies are limited by the difficulty of obtaining cells taken directly from their tissue environment, relying instead on eosinophils isolated from peripheral blood. Isolation techniques for tissue-derived eosinophils can result in unwanted cell or ribonuclease activation, leading to poor cell viability or RNA quality, which may impair analysis of effector activities of these cells. Here we demonstrate a technique to obtain eosinophils from human adipose tissue samples for the purpose of downstream molecular analysis. From as little as 2 g of intact human adipose tissue, greater than 104 eosinophils were purified by fluorescence-activated cell sorting (FACS) protocol resulting in ≥ 99% purity and ≥ 95% viable eosinophils. We demonstrated that the isolated eosinophils could undergo epigenetic analysis to determine differences in DNA methylation in various settings. Here we focused on comparing eosinophils isolated from human peripheral blood vs human adipose tissue. Our results open the door to future mechanistic investigations to better understand the role of tissue resident eosinophils in different context.

Inorganic Nitrate Promotes Glucose Uptake and Oxidative Catabolism in White Adipose Tissue Through the XOR-Catalyzed Nitric Oxide Pathway.

An aging global population combined with sedentary lifestyles and unhealthy diets has contributed to an increasing incidence of obesity and type 2 diabetes. These metabolic disorders are associated with perturbations to nitric oxide (NO) signaling and impaired glucose metabolism. Dietary inorganic nitrate, found in high concentration in green leafy vegetables, can be converted to NO in vivo and demonstrates antidiabetic and antiobesity properties in rodents. Alongside tissues including skeletal muscle and liver, white adipose tissue is also an important physiological site of glucose disposal. However, the distinct molecular mechanisms governing the effect of nitrate on adipose tissue glucose metabolism and the contribution of this tissue to the glucose-tolerant phenotype remain to be determined. Using a metabolomic and stable-isotope labeling approach, combined with transcriptional analysis, we found that nitrate increases glucose uptake and oxidative catabolism in primary adipocytes and white adipose tissue of nitrate-treated rats. Mechanistically, we determined that nitrate induces these phenotypic changes in primary adipocytes through the xanthine oxidoreductase-catalyzed reduction of nitrate to NO and independently of peroxisome proliferator-activated receptor-α. The nitrate-mediated enhancement of glucose uptake and catabolism in white adipose tissue may be a key contributor to the antidiabetic effects of this anion.

PET imaging during hypoglycaemia to study adipose tissue metabolism.

BackgroundDisturbances in adipose tissue glucose uptake may play a role in the pathogenesis of type 2 diabetes, yet its examination by 2‐deoxy‐2‐[18F]fluorodeoxyglucose ([18F]FDG) PET/CT is challenged by relatively low uptake kinetics. We tested the hypothesis that performing [18F]FDG PET/CT during a hypoglycaemic clamp would improve adipose tissue tracer uptake to allow specific comparison of adipose tissue glucose handling between people with or without type 2 diabetes.DesignWe enrolled participants with or without diabetes who were at least overweight, to undergo a hyperinsulinaemic hypoglycaemic clamp or a hyperinsulinaemic euglycaemic clamp (n = 5 per group). Tracer uptake was quantified using [18F]FDG PET/CT.ResultsHypoglycaemic clamping increased [18F]FDG uptake in visceral adipose tissue of healthy participants (P = 0.002). During hypoglycaemia, glucose uptake in visceral adipose tissue of type 2 diabetic participants was lower as compared to healthy participants (P < 0.0005). No significant differences were observed in skeletal muscle, liver or pancreas.ConclusionsThe present findings indicate that [18F]FDG PET/CT during a hypoglycaemic clamp provides a promising new research tool to evaluate adipose tissue glucose metabolism. Using this method, we observed a specific impairment in visceral adipose tissue [18F]FDG uptake in type 2 diabetes, suggesting a previously underestimated role for adipose tissue glucose handling in type 2 diabetes.

GSK3\u03b2 inhibition attenuates LPS-induced IL-6 expression in porcine adipocytes

IL-6 is not only a proinflammatory cytokine associated with inflammatory responses but also a regulator on the energy and glucose metabolism in adipose tissue. Glycogen synthase kinase 3β (GSK3β) has fundamental roles in the regulation of pro- and anti-inflammatory cytokines production. However, the regulatory role for GSK3β in the pig inflammatory response in adipocytes remains unknown. We show here that SB216763 and LPS increased the phosphorylation of GSK3β (Ser9), and decreased the phosphorylation of GS (Ser641) in adipocytes. The activity of porcine GSK3β was inhibited by SB216763, an inhibitor of GSK3β, attenuated the production of IL-6 in LPS-stimulated adipocytes. Additionally, the essential core region of the pig IL-6 promoter located at −191 bp to −59 bp, and an NF-κBp65 element in this region was responsible for IL-6 promoter activity. The transcription activity of NF-κBp65 was activated by LPS stimulation, and the GSK3β inhibition repressed LPS-induced luciferase activity of the IL-6 promoter. Furthermore, LPS increased p65 binding to the NF-κB site, and GSK3β inhibition had no effect on the association of NF-κBp65 with IL-6 gene promoter after LPS treatment. These results demonstrate that GSK3β has important regulatory roles in the LPS-induced inflammatory response of IL-6 production in pig adipocytes.

Residual feed intake phenotype and gender affect the expression of key genes of the lipogenesis pathway in subcutaneous adipose tissue of beef cattle

BackgroundFeed accounts for up to 75% of costs in beef production systems, thus any improvement in feed efficiency (FE) will benefit the profitability of this enterprise. Residual feed intake (RFI) is a measure of FE that is independent of level of production. Adipose tissue (AT) is a major endocrine organ and the primary metabolic energy reservoir. It modulates a variety of processes related to FE such as lipid metabolism and glucose homeostasis and thus measures of inter-animal variation in adiposity are frequently included in the calculation of the RFI index. The aim of this study was to determine the effect of phenotypic RFI status and gender on the expression of key candidate genes related to processes involved in energy metabolism within AT. Dry matter intake (DMI) and average daily gain (ADG) were measured over a period of 70 d for 52 purebred Simmental heifers (n = 24) and bulls (n = 28) with an initial BW±SD of 372±39.6 kg and 387±50.6 kg, respectively. Residual feed intake was calculated and animals were ranked within gender by RFI into high (inefficient; n = 9 heifers and n = 8 bulls) and low (efficient; n = 9 heifers and n = 8 bulls) groups.ResultsAverage daily gain ±SD and daily DMI ±SD for heifers and bulls were 1.2±0.4 kg and 9.1±0.5 kg, and 1.8±0.3 kg and 9.5±1 kg respectively. High RFI heifers and bulls consumed 10% and 15% more (P < 0.05) than their low RFI counterparts, respectively. Heifers had a higher expression of all genes measured than bulls (P < 0.05). A gender × RFI interaction was detected for HMGCS2(P < 0.05) in which high RFI bulls tended to have lower expression of HMGCS2 than low RFI bulls (P < 0.1), whereas high RFI heifers had higher expression than low RFI heifers (P < 0.05) and high RFI bulls (P < 0.05). SLC2A4 expression was consistently higher in subcutaneous AT of low RFI animals across gender.ConclusionThe findings of this study indicate that low RFI cattle exhibit upregulation of the molecular mechanisms governing glucose metabolism in adipose tissue, in particular, glucose clearance. The decreased expression of SLC2A4 in the inefficient cattle may result in less efficient glucose metabolism in these animals. We conclude that SLC2A4 may be a potential biomarker for RFI in cattle.

Deletion of PHGDH in adipocytes improves glucose intolerance in diet-induced obese mice

Serine is a nonessential amino acid and plays an important role in cellular metabolism. In mammalian serine biosynthesis, 3-phosphoglycerate dehydrogenase (PHGDH) is considered a rate-limiting enzyme and is required for normal development. Although the biological functions of PHGHD in the nervous system have been intensively studied, its function in adipose tissue is unknown. In this study, we found that PHGDH is abundantly expressed in mature adipocytes of white adipose tissue. We generated an adipocyte-specific PHGDH knockout mouse (PHGDH FKO) and used it to investigate the role of serine biosynthesis in adipose tissues. Although PHGDH FKO mice had no apparent defects in adipose tissue development, these mice ameliorated glucose intolerance upon diet-induced obesity. Additionally, we found that the serine levels increase drastically in the adipose tissues of obese wild type mice, whereas no significant rise was observed in PHGDH FKO mice. Furthermore, wild type mice fed a serine-deficient diet also exhibited better glucose tolerance. These results suggest that PHGDH-mediated serine biosynthesis has important roles in adipose tissue glucose metabolism and could be a therapeutic target for diabetes in humans.

Calcium and Magnesium Urinary Excretion in Dairy Cows with Different Fee of Glucose Metabolization

Background: The post-partum period in dairy cows is accompanied by a low glucose metabolism in adipose tissue and skeletal muscle tissue, being glucose conducted to the milk production. In humans, low glucose metabolism is associated with metabolic syndromes, the high glucose levels reduce tubular reabsorption of Magnesium (Mg) and Calcium (Ca), leading to hypomagnesemia and hypocalcemia. These minerals are important to the dairy cow, as their decrease leads to diseases. The aim of this study was to evaluate the relationship between glucose metabolism rate with the urinary excretion of Ca and Mg in multiparous dairy cows during the post-partum period.Materials, Methods &amp; Results: Twenty dairy cows were used from a commercial farm southern Brazil, in the semi-extensive system. Glucose tolerance tests were performed (TTG) on day 9 relative to calving. The cows were categorized into three groups according to the glucose metabolism rate (area under the glucose curve, glucose half-life and glucose consumption rate): High Glucose Metabolization (GA); Intermediate Glucose Metabolizing (GI); and Low Glucose Metabolization (GL). Blood and urine samples were collected on days 0, + 3, + 6, + 9, +16 and +2 3 in relation to calving for to determine the levels of Ca, Mg, insulin (Ins), non-esterified fatty acids (NEFA) and Glu. In urine was evaluated the excretion of Ca and Mg. The cows were milked twice a day (at 3:00 a.m. and 3:00 p.m.) and the milk yield (kg/cow) was recorded daily and averages were generated every five days from day 15 to day 60 postpartum. The statistical analyses were performed with the MIXED procedure to assess the main effect of group, time (in days) and their interaction by using version 9.2 SAS software. The influence of the different rates of glucose metabolism on milk production was observed, the GB group had a production than GH group (30.88 ± 1.44 kg vs 23.96 ± 1.43 kg, P &lt; 0.01), but did not differ from GI. The GL group showed higher levels of Glu compared to GA (P &lt; 0.05). The plasma Ca levels were higher in GL (P &lt; 0.05) compared with GH. The NEFA, insulin, and excretion of minerals did not differ between groups (P &gt; 0.05).Discussion: The low glucose metabolism in humans causes an increase in the excretion of Ca and Mg urine, however, in the animals studied, these changes were not observed. This result can be attributed to the fact that insulin resistance is transitory in dairy cattle. The higher glucose levels in the GL group are related due to the lower capacity of glucose entry in the peripheral tissues (adipose and skeletal muscle), which reflected in the higher milk production observed this group. However, the higher calcium concentrations were not expected, since the release of insulin by β-pancreatic cells is dependent on calcium. Possibly, these higher calcium levels in GB, are related to higher milk production, requiring a greater amount of calcium for the production of casein, increasing bone mobilization, intestinal absorption. The energy metabolites, non-esterified fatty acids and insulin, did not differ between groups, suggesting that the animals did not present different metabolic conditions. We conclude that multiparous dairy cows with low glucose metabolism rate (GB) have higher levels of glucose after delivery and increased milk production. The metabolism rate of glucose did not influence the excretion of the Ca and Mg minerals.

Okara ameliorates glucose tolerance in GK rats

Okara, a food by-product from the production of tofu and soy milk, is rich in three beneficial components: insoluble dietary fiber, β-conglycinin, and isoflavones. Although isoflavones and β-conglycinin have recently been shown to improve glucose tolerance, the effects of okara have not yet been elucidated. Therefore, we herein investigated the effects of okara on glucose tolerance in Goto-Kakizaki (GK) rats, a representative animal model of Japanese type 2 diabetes. Male GK rats were fed a 10% lard diet with or without 5% dry okara powder for 2 weeks and an oral glucose tolerance test was performed. Rats were then fed each diet for another week and sacrificed. The expression of genes that are the master regulators of glucose metabolism in adipose tissue was subsequently examined. No significant differences were observed in body weight gain or food intake between the two groups of GK rats. In the oral glucose tolerance test, increases in plasma glucose levels were suppressed by the okara diet. The mRNA expression levels of PPARγ, adiponectin, and GLUT4, which up-regulate the effects of insulin, were increased in epididymal adipose tissue by the okara diet. These results suggest that okara provides a useful means for treating type 2 diabetes.

Effect of Bariatric Surgery on Adipose Tissue Glucose Metabolism in Different Depots in Patients With or Without Type 2 Diabetes.

We investigated fat distribution and tissue-specific insulin-stimulated glucose uptake (GU) in seven fat compartments (visceral and subcutaneous) and skeletal muscle in morbidly obese patients with (T2D) and without (ND) type 2 diabetes before and 6 months after bariatric surgery. A total of 23 obese patients (BMI 43.0 ± 3.6 kg/m(2); 9 T2D and 14 ND) were recruited from a larger, randomized multicenter SLEEVEPASS study. MRI (for fat distribution) and [(18)F]-fluorodeoxyglucose PET (for GU) studies were performed for the obese patients before and 6 months postsurgery; 10 lean subjects served as control subjects and were studied once. At baseline, visceral fat GU was 30 ± 7% of muscle GU in control subjects and 57 ± 5% in obese patients. Visceral and deep subcutaneous fat were more abundant (despite same total fat mass) and less insulin sensitive in T2D than ND; in both, GU was impaired compared with control subjects. Postsurgery, visceral fat mass decreased (∼40%) more than subcutaneous fat (7%). Tissue-specific GU was improved, but not normalized, at all sites in T2D and ND alike. The contribution of visceral fat to whole-body GU was greater in T2D than ND but decreased similarly with surgery. Subcutaneous fat made a fourfold greater contribution to whole-body GU in obese versus lean subjects (15% vs. 4%) both before and after surgery. Bariatric surgery leads to sustained weight loss and improves tissue-specific glucose metabolism in morbidly obese patients. We conclude that 1) enhanced visceral fat accumulation is a feature of T2D, 2) severe obesity compromises muscle insulin sensitivity more than fat insulin sensitivity, and 3) fat mass expansion is a sink for plasma glucose.

Physiological Roles of Adipokines, Hepatokines, and Myokines in Ruminants.

Since the discovery of leptin secreted from adipocytes, specialized tissues and cells have been found that secrete the several peptides (or cytokines) that are characterized to negatively and positively regulate the metabolic process. Different types of adipokines, hepatokines, and myokines, which act as cytokines, are secreted from adipose, liver, and muscle tissue, respectively, and have been identified and examined for their physiological roles in humans and disease in animal models. Recently, various studies of these cytokines have been conducted in ruminants, including dairy cattle, beef cattle, sheep, and goat. Interestingly, a few cytokines from these tissues in ruminants play an important role in the post-parturition, lactation, and fattening (marbling) periods. Thus, understanding these hormones is important for improving nutritional management in dairy cows and beef cattle. However, to our knowledge, there have been no reviews of the characteristics of these cytokines in beef and dairy products in ruminants. In particular, lipid and glucose metabolism in adipose tissue, liver tissue, and muscle tissue are very important for energy storage, production, and synthesis, which are regulated by these cytokines in ruminant production. In this review, we summarize the physiological roles of adipokines, hepatokines, and myokines in ruminants. This discussion provides a foundation for understanding the role of cytokines in animal production of ruminants.