scholarly journals Countering impaired glucose homeostasis during catch-up growth with essential polyunsaturated fatty acids: is there a major role for improved insulin sensitivity?

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Julie Calonne ◽  
Helena Marcelino ◽  
Christelle Veyrat-Durebex ◽  
Isabelle Scerri ◽  
Abdul G. Dulloo
Keyword(s):  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Skeletal Muscles ◽  
Glucose Utilization ◽  
Whole Body ◽  
High Fat ◽  
Adipose Tissue Depots ◽  
Body Level ◽  
Catch Up

Abstract Background/Objectives Catch-up growth, an important risk factor for later obesity and type 2 diabetes, is often characterized by a high rate of fat deposition associated with hyperinsulinemia and glucose intolerance. We tested here the hypothesis that refeeding on a high-fat diet rich in essential polyunsaturated fatty acids (ePUFA) improves glucose homeostasis primarily by enhancing insulin sensitivity in skeletal muscles and adipose tissues. Methods Rats were caloric restricted for 2 weeks followed by 1–2 weeks of isocaloric refeeding on either a low-fat (LF) diet, a high-fat (HF) diet based on animal fat and high in saturated and monounsaturated fatty acids (HF SMFA diet), or a HF diet based on vegetable oils (1:1 mixture of safflower and linseed oils) and rich in the essential fatty acids linoleic and α-linolenic acids (HF ePUFA diet). In addition to measuring body composition and a test of glucose tolerance, insulin sensitivity was assessed during hyperinsulinemic-euglycemic clamps at the whole-body level and in individual skeletal muscles and adipose tissue depots. Results Compared to animals refed the LF diet, those refed the HF-SMFA diet showed a higher rate of fat deposition, higher plasma insulin and glucose responses during the test of glucose tolerance, and markedly lower insulin-stimulated glucose utilization at the whole body level (by a-third to a-half) and in adipose tissue depots (by 2–5 folds) during insulin clamps. While refeeding on the ePUFA diet prevented the increases in fat mass and in plasma insulin and glucose, the results of insulin clamps revealed that insulin-stimulated glucose utilization was not increased in skeletal muscles and only marginally higher in adipose tissues and at the whole-body level. Conclusions These results suggest only a minor role for enhanced insulin sensitivity in the mechanisms by which diets high in ePUFA improves glucose homeostasis during catch-up growth.

scholarly journals ANGPTL4 from adipose, but not liver, is responsible for regulating plasma triglyceride partitioning

2020 ◽  
Author(s):  
Kathryn M. Spitler ◽  
Shwetha K. Shetty ◽  
Emily M. Cushing ◽  
Kelli L. Sylvers-Davie ◽  
Brandon S.J. Davies
Keyword(s):  
Metabolic Disease ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Plasma Triglyceride ◽  
Whole Body ◽  
Elevated Plasma ◽  
High Fat ◽  
Deficient Mice

ABSTRACTElevated plasma triglyceride levels are associated with metabolic disease. Angiopoietin-like protein 4 (ANGPTL4) regulates plasma triglyceride levels by inhibiting lipoprotein lipase (LPL). Our aim was to investigate the role of tissue-specific ANGPTL4 expression in the setting of high fat diet. Adipocyte- and hepatocyte-specific ANGPTL4 deficient mice were fed a high fat diet (60% kCal from fat) for either 12 weeks or 6 months. We performed plasma metabolic measurements, triglyceride clearance and uptake assays, LPL activity assays, and assessed glucose homeostasis. Mice lacking adipocyte ANGPTL4 recapitulated the triglyceride phenotypes of whole-body ANGPTL4 deficiency, whereas mice lacking hepatocyte ANGPTL4 had few triglyceride phenotypes. When fed a high fat diet (HFD), mice deficient in adipocyte ANGPTL4 gained more weight, had enhanced adipose LPL activity, and initially had improved glucose and insulin sensitivity. However, this improvement was largely lost after 6 months on HFD. Conversely, mice deficient in hepatocyte ANGPTL4 initially displayed no differences in glucose homeostasis, but began to manifest improved glucose tolerance after 6 months on HFD. We conclude that it is primarily adipocyte-derived ANGPTL4 that is responsible for regulating plasma triglyceride levels. Deficiency in adipocyte- or hepatocyte-derived ANGPTL4 may confer some protections against high fat diet induced dysregulation of glucose homeostasis.

Impact of human visceral and glutealfemoral adipose tissue transplant on glycemic control in a mouse model of diet-induced obesity

2020 ◽  
Vol 319 (3) ◽  
pp. E519-E528
Author(s):  
Thomas Tsiloulis ◽  
Arthe Raajendiran ◽  
Stacey N. Keenan ◽  
Geraldine Ooi ◽  
Renea A. Taylor ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glycemic Control ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Fasting Blood Glucose ◽  
Whole Body ◽  
High Fat ◽  
Positive Effects ◽  
Tissue Transplant

Regional distribution of adipose tissue is an important factor in conferring cardiometabolic risk and obesity-related morbidity. We tested the hypothesis that human visceral adipose tissue (VAT) impairs glucose homeostasis, whereas subcutaneous glutealfemoral adipose tissue (GFAT) protects against the development of impaired glucose homeostasis in mice. VAT and GFAT were collected from patients undergoing bariatric surgery and grafted onto the epididymal adipose tissue of weight- and age-matched severe, combined immunodeficient mice. SHAM mice underwent surgery without transplant of tissue. Mice were fed a high-fat diet after xenograft. Energy homeostasis, glucose metabolism, and insulin sensitivity were assessed 6 wk later. Xenograft of human adipose tissues was successful, as determined by histology, immunohistochemical evaluation of collagen deposition and angiogenesis, and maintenance of lipolytic function. Adipose tissue transplant did not affect energy expenditure, food intake, whole body substrate partitioning, or plasma free fatty acid, triglyceride, and insulin levels. Fasting blood glucose was significantly reduced in GFAT and VAT compared with SHAM, whereas glucose tolerance was improved only in mice transplanted with VAT compared with SHAM mice. This improvement was not associated with differences in whole body insulin sensitivity or plasma insulin between groups. Together, these data suggest that VAT improves glycemic control and GFAT does not protect against the development of high-fat diet-induced glucose intolerance. Hence, the intrinsic properties of VAT and GFAT do not necessarily explain the postulated negative and positive effects of these adipose tissue depots on metabolic health.

scholarly journals Sex-specific programming of adult insulin resistance in guinea pigs by variable perinatal growth induced by spontaneous variation in litter size

2019 ◽  
Vol 316 (4) ◽  
pp. R352-R361
Author(s):  
Dane M. Horton ◽  
David A. Saint ◽  
Kathryn L. Gatford ◽  
Karen L. Kind ◽  
Julie A. Owens
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Guinea Pigs ◽  
Glucose Utilization ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Catch Up ◽  
Endogenous Glucose

Intrauterine growth restriction (IUGR) and subsequent neonatal catch-up growth are implicated in programming of insulin resistance later in life. Spontaneous IUGR in the guinea pig, due to natural variation in litter size, produces offspring with asymmetric IUGR and neonatal catch-up growth. We hypothesized that spontaneous IUGR and/or accelerated neonatal growth would impair insulin sensitivity in adult guinea pigs. Insulin sensitivity of glucose metabolism was determined by hyperinsulinemic-euglycemic clamp (HEC) in 38 (21 male, 17 female) young adult guinea pigs from litters of two-to-four pups. A subset (10 male, 8 female) were infused with d-[3-3H]glucose before and during the HEC to determine rates of basal and insulin-stimulated glucose utilization, storage, glycolysis, and endogenous glucose production. n males, the insulin sensitivity of whole body glucose uptake ( r = 0.657, P = 0.002) and glucose utilization ( r = 0.884, P = 0.004) correlated positively and independently with birth weight, but not with neonatal fractional growth rate (FGR10–28). In females, the insulin sensitivity of whole body and partitioned glucose metabolism was not related to birth weight, but that of endogenous glucose production correlated negatively and independently with FGR10–28 ( r = −0.815, P = 0.025). Thus, perinatal growth programs insulin sensitivity of glucose metabolism in the young adult guinea pig and in a sex-specific manner; impaired insulin sensitivity, including glucose utilization, occurs after IUGR in males and impaired hepatic insulin sensitivity after rapid neonatal growth in females.

scholarly journals Effects of dietary propionate on hepatic glucose production, whole-body glucose utilization, carbohydrate and lipid metabolism in normal rats

1995 ◽  
Vol 73 (2) ◽  
pp. 241-251 ◽  
Author(s):  
Josette Boillot ◽  
Catherine Alamowitch ◽  
Anne-Marie Berger ◽  
Jing Luo ◽  
Françoise Bruzzo ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Glucose Utilization ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Whole Body ◽  
Dietary Fibres ◽  
Carbohydrate And Lipid Metabolism ◽  
Hepatic Glucose ◽  
Anaesthetized Rats

Increased intake of dietary fibres is associated with several beneficial effects on carbohydrate and lipid metabolism. The colonic fermentation of dietary fibres produces short-chain fatty acids (SCFA; acetate, propionate and butyrate). Some authors have suggested that SCFA could be partly responsible for the effects of dietary fibres. The purpose of the present study was to test the effects of one of the SCFA, propionate. The effects of moderate amounts of dietary propionate on insulin sensitivity and hepatic glucose production were studied in male Sprague-Dawley rats. Two groups of twenty-one adult rats were fed for 3 weeks on a diet containing 78 g propionate/kg (P) or 78 g/kg of a poorly fermentable cellulose (control group; C). Feed intake, body weight, fasting plasma glucose, insulin, free fatty acids, alanine, lactate, glycerol and β-hydroxybutyrate levels were measured weekly in anaesthetized rats. At the end of the feeding period basal hepatic glucose production (BHGP) was measured with a primed continuous infusion of [3−3H]glucose and the in vivo insulin sensitivity in rats was quantified by the euglycaemic-hyperinsulinaemic clamp technique (0.6 and 2 U/kg per h). At that time fasting plasma glucose measured in anaesthetized rats was significantly lower in group P than in group C: 7·7 (SE 0·2) v. 8.5 (SE 0·2) mmol/l respectively (P < 0·002); plasma insulin levels were not significantly different. Neither the BHGP (mg/min per kg; C 14·8 (SE 1·3), P 15·1 (SE 1·3); n 7, not significant) nor the basal metabolic clearance (ml/min per kg; 8·9 (SE 08) v. 9·9 (SE 1·1); not significant) were different between treatments. Hepatic glucose production and glucose utilization at the two insulin concentrations (approximately 500 and 1500 mU/l respectively, n 7) did not differ significantly between the two groups. These results show that dietary propionate chronically ingested by normal rats could decrease fasting glycaemia, but from our findings, no effect on hepatic glucose production and whole-body glucose utilization could be clearly demonstrated.

scholarly journals Genetic Deletion of Syndecan-4 Alters Body Composition, Metabolic Phenotypes, and the Function of Metabolic Tissues in Female Mice Fed A High-Fat Diet (Running Title: Sdc4 Deficiency Affects Metabolic Phenotypes)

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2810 ◽  
Author(s):  
Maria De Luca ◽  
Denise Vecchie’ ◽  
Baskaran Athmanathan ◽  
Sreejit Gopalkrishna ◽  
Jennifer A. Valcin ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Serum Triglyceride ◽  
Independent Study ◽  
Whole Body ◽  
Elderly Subjects ◽  
Sensitivity Index ◽  
High Fat ◽  
Metabolic Phenotypes

Syndecans are transmembrane proteoglycans that, like integrins, bind to components of the extracellular matrix. Previously, we showed significant associations of genetic variants in the Syndecan-4 (SDC4) gene with intra-abdominal fat, fasting plasma glucose levels, and insulin sensitivity index in children, and with fasting serum triglyceride levels in healthy elderly subjects. An independent study also reported a correlation between SDC4 and the risk of coronary artery disease in middle-aged patients. Here, we investigated whether deletion of Sdc4 promotes metabolic derangements associated with diet-induced obesity by feeding homozygous male and female Sdc4-deficient (Sdc4-/-) mice and their age-matched wild-type (WT) mice a high-fat diet (HFD). We found that WT and Sdc4-/- mice gained similar weight. However, while no differences were observed in males, HFD-fed female Sdc4-/- mice exhibited a higher percentage of body fat mass than controls and displayed increased levels of plasma total cholesterol, triglyceride, and glucose, as well as reduced whole-body insulin sensitivity. Additionally, they had an increased adipocyte size and macrophage infiltration in the visceral adipose tissue, and higher triglyceride and fatty acid synthase levels in the liver. Together with our previous human genetic findings, these results provide evidence of an evolutionarily conserved role of SDC4 in adiposity and its complications.

scholarly journals Increased Insulin Sensitivity by High-Altitude Hypoxia in Mice with High-Fat Diet-Induced Obesity Is Associated with Activated AMPK Signaling and Subsequently Enhanced Mitochondrial Biogenesis in Skeletal Muscles

Obesity Facts ◽  
2020 ◽  
Vol 13 (5) ◽  
pp. 455-472
Author(s):  
Kang Song ◽  
Yifan Zhang ◽  
Qin Ga ◽  
Zhenzhong Bai ◽  
Ri-Li Ge
Keyword(s):  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Protein Kinase ◽  
High Altitude ◽  
Mitochondrial Biogenesis ◽  
High Fat Diet ◽  
Skeletal Muscles ◽  
Acid Oxidation ◽  
High Fat ◽  
Low Altitude

<b><i>Background:</i></b> This study aimed to investigate whether and how high altitude-associated ambient hypoxia affects insulin sensitivity in mice fed a high-fat diet (HFD). <b><i>Methods:</i></b> Mice were randomly divided into a control group (with normal diet feeding and low-altitude housing), LA/HFD group (with HFD feeding and low-altitude housing), and HA/HFD group (with HFD feeding and high-altitude housing). <b><i>Results:</i></b> After 8 weeks, mice in the HA/HFD group showed improved insulin sensitivity-related indices compared with the LA/HFD group. In mice residing in a low-altitude region, HFD significantly impaired mitochondrial respiratory function and mitochondrial DNA content in skeletal muscles, which was partially reversed in mice in the HA/HFD group. In addition, the fatty acid oxidation-related enzyme gene <i>CPT1</i> (carnitine palmitoyltransferase 1) and genes related to mitochondrial biogenesis such as peroxisome proliferator-activated receptor-γ coactivator-1α (<i>PGC-1α</i>), nuclear respiratory factor 1 (<i>NRF1</i>), and mitochondrial transcription factor A (<i>Tfam</i>) were upregulated in the skeletal muscles of mice housed at high altitude, in comparison to in the LA/HFD group. Furthermore, AMPK (adenosine monophosphate-activated protein kinase) signaling was activated in the skeletal muscles, as evidenced by a higher expression of phosphorylated AMPK (p-AMPK) and protein kinase B (p-AKT) in the HA/HFD group than in the LA/HFD group. <b><i>Conclusion:</i></b> Our study suggests that high-altitude hypoxia improves insulin sensitivity in mice fed an HFD, which is associated with AMPK activation in the skeletal muscle and consequently enhanced mitochondrial biogenesis and fatty acid oxidation. This work provides a molecular explanation for why high altitude is associated with a reduced incidence of insulin resistance in the obese population.

Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites

2006 ◽  
Vol 100 (5) ◽  
pp. 1467-1474 ◽  
Author(s):  
Jong Sam Lee ◽  
Srijan K. Pinnamaneni ◽  
Su Ju Eo ◽  
In Ho Cho ◽  
Jae Hwan Pyo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Polyunsaturated Fatty Acids ◽  
Glucose Uptake ◽  
High Fat ◽  
Insulin Resistant ◽  
L6 Myotubes ◽  
Lipid Metabolites

Consumption of a Western diet rich in saturated fats is associated with obesity and insulin resistance. In some insulin-resistant phenotypes this is associated with accumulation of skeletal muscle fatty acids. We examined the effects of diets high in saturated fatty acids (Sat) or n-6 polyunsaturated fatty acids (PUFA) on skeletal muscle fatty acid metabolite accumulation and whole-body insulin sensitivity. Male Sprague-Dawley rats were fed a chow diet (16% calories from fat, Con) or a diet high (53%) in Sat or PUFA for 8 wk. Insulin sensitivity was assessed by fasting plasma glucose and insulin and glucose tolerance via an oral glucose tolerance test. Muscle ceramide and diacylglycerol (DAG) levels and triacylglycerol (TAG) fatty acids were also measured. Both high-fat diets increased plasma free fatty acid levels by 30%. Compared with Con, Sat-fed rats were insulin resistant, whereas PUFA-treated rats showed improved insulin sensitivity. Sat caused a 125% increase in muscle DAG and a small increase in TAG. Although PUFA also resulted in a small increase in DAG, the excess fatty acids were primarily directed toward TAG storage (105% above Con). Ceramide content was unaffected by either high-fat diet. To examine the effects of fatty acids on cellular lipid storage and glucose uptake in vitro, rat L6 myotubes were incubated for 5 h with saturated and polyunsaturated fatty acids. After treatment of L6 myotubes with palmitate (C16:0), the ceramide and DAG content were increased by two- and fivefold, respectively, concomitant with reduced insulin-stimulated glucose uptake. In contrast, treatment of these cells with linoleate (C18:2) did not alter DAG, ceramide levels, and glucose uptake compared with controls (no added fatty acids). Both 16:0 and 18:2 treatments increased myotube TAG levels (C18:2 vs. C16:0, P < 0.05). These results indicate that increasing dietary Sat induces insulin resistance with concomitant increases in muscle DAG. Diets rich in n-6 PUFA appear to prevent insulin resistance by directing fat into TAG, rather than other lipid metabolites.

Whole body insulin sensitivity in Osborne-Mendel and S 5B/Pl rats eating a low- or high-fat diet

1992 ◽  
Vol 263 (4) ◽  
pp. R785-R789 ◽  
Author(s):  
T. A. Buchanan ◽  
J. S. Fisler ◽  
S. Underberger ◽  
G. F. Sipos ◽  
G. A. Bray
Keyword(s):  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Whole Body ◽  
High Fat ◽  
Low Fat ◽  
Low Fat Diet ◽  
High Fat Diets ◽  
Glucose Clearance ◽  
Fat Diets ◽  
Fat Feeding

To determine whether whole body insulin sensitivity differs between a rat strain that does not (S 5B/Pl) and a strain that does [Osborne-Mendel (OM)] become obese when eating a high-fat diet, we performed euglycemic clamp studies in animals from each strain during low- and high-fat feeding. Clamps were performed after 2 days ("initial clamp") and 9 days ("final clamp") on each diet. Plasma glucose and insulin levels during the final 60 min of initial and final clamps were similar in S 5B/Pl and OM rats regardless of diet. Insulin sensitivity, measured as the glucose clearance rate during the final 60 min of the clamp, averaged 35 +/- 3 ml.kg-1.min-1 in S 5B/Pl rats after 2 days on a low-fat diet. This did not change significantly during an additional 7 days on the low-fat diet. The high-fat diet was associated with a 13% reduction in insulin sensitivity after 2 days and a 30% reduction after 9 days in S 5B/Pl rats. OM rats exhibited similar patterns of insulin sensitivity during low- and high-fat diets, albeit at lower insulin sensitivity overall (P < 0.0005 vs. S 5B/Pl). Mean glucose clearance after 2 days on the low-fat diet was 27 +/- 2 mg.kg-1.min-1 and did not change significantly during seven more days of low-fat feeding. The high-fat diet was associated with a 19% reduction in glucose clearance after 2 days and a 38% reduction after 9 days in OM rats. The magnitude of reduction in insulin sensitivity during high-fat diets did not differ significantly between strains.(ABSTRACT TRUNCATED AT 250 WORDS)

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