scholarly journals Adipocyte Gi signaling is essential for maintaining whole-body glucose homeostasis and insulin sensitivity

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Lei Wang ◽  
Sai P. Pydi ◽  
Lu Zhu ◽  
Luiz F. Barella ◽  
Yinghong Cui ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Whole Body

scholarly journals Incorporation of Unique, Diet-derived Fatty Acids into Hepatic Tissue Is Associated with Improved Glucose Homeostasis in Aged CD-1 Mice (OR24-02-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Allison Unger ◽  
Thomas Jetton ◽  
James Whitley ◽  
Jana Kraft
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Whole Body ◽  
Hepatic Tissue ◽  
Gas Liquid Chromatography ◽  
Mouse Population ◽  
Echium Oil ◽  
Dairy Fat ◽  
Fa Composition

Abstract Objectives We hypothesized that the chronic consumption of unique dietary FA derived from dairy fat and echium oil, respectively, would affect the FA composition and content of the hepatic tissue and correlate with parameters of glucose homeostasis in an aged, genetically heterogeneous mouse population. Our objectives were to i) measure glucose homeostasis, ii) determine the FA composition of hepatic tissue, and iii) correlate physiologic data and hepatic FA content by diet and sex. Methods From one month of age, CD-1 male and female mice (n = 10/diet/sex) were fed either a high-fat (40% total energy) control diet comprising of the FA composition of the typical U.S. American diet (CO), or an isoenergetic diet with 30% of CO fat replaced with dairy fat (BO) or echium oil (EO) for the study duration of 13 months. Every three months, whole-body glucose homeostasis was assessed (i.e., glucose tolerance and insulin tolerance tests (GTT and ITT, respectively)). At the end of the study, hepatic tissue was collected and analyzed for FA composition via gas-liquid chromatography. Results Hepatic content of stearidonic acid (SDA; 18:4 n-3) and γ-linolenic acid (18:3 n-6) was greatest in EO-fed mice (P < .0001). Mice fed a BO-diet had the greatest hepatic content of total odd- and branched-chain FA (OBCFA) and conjugated linoleic acids (P < .0001), as well as a greater hepatic content of 18:1 isomers compared to EO-fed mice (P < .001). In EO-fed females, hepatic content of SDA correlated with improved glucose tolerance, as determined by GTT area under the curve (r = −.94; P < 0.01), and in EO-fed males, hepatic content of SDA was positively associated with improved insulin sensitivity (r = .79; P < 0.05). In BO-fed males, hepatic content of total OCFA was negatively correlated with fasting plasma insulin levels (r = −.83; P < 0.05), and hepatic content of total iso BCFA was associated with improved insulin sensitivity (r = −.89; P < 0.05). Conclusions These findings demonstrate that habitual consumption of unique FA derived from dairy fat and echium oil influences hepatic FA composition and content and correlates with improvements in whole-body glucose homeostasis in an aged population. Furthermore, this study suggests that dietary fat quality may be part of an effective preventative strategy for metabolic diseases such as T2D in the elderly. Funding Sources Armin Grams Memorial Research Award, UVM Robert Larner, M.D. College of Medicine; USDA-NIFA Hatch Fund (accession number: 1006628).

scholarly journals Brown Adipose Tissue Improves Whole-Body Glucose Homeostasis and Insulin Sensitivity in Humans

Diabetes ◽  
2014 ◽  
Vol 63 (12) ◽  
pp. 4089-4099 ◽  
Author(s):  
M. Chondronikola ◽  
E. Volpi ◽  
E. Borsheim ◽  
C. Porter ◽  
P. Annamalai ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Brown Adipose Tissue ◽  
Glucose Homeostasis ◽  
Whole Body ◽  
Brown Adipose

scholarly journals Astrocyte Clocks and Glucose Homeostasis

2021 ◽  
Vol 12 ◽  
Author(s):  
Olga Barca-Mayo ◽  
Miguel López
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Circadian Clock ◽  
Glucose Homeostasis ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Genetic Alterations ◽  
Whole Body

The endogenous timekeeping system evolved to anticipate the time of the day through the 24 hours cycle of the Earth’s rotation. In mammals, the circadian clock governs rhythmic physiological and behavioral processes, including the daily oscillation in glucose metabolism, food intake, energy expenditure, and whole-body insulin sensitivity. The results from a series of studies have demonstrated that environmental or genetic alterations of the circadian cycle in humans and rodents are strongly associated with metabolic diseases such as obesity and type 2 diabetes. Emerging evidence suggests that astrocyte clocks have a crucial role in regulating molecular, physiological, and behavioral circadian rhythms such as glucose metabolism and insulin sensitivity. Given the concurrent high prevalence of type 2 diabetes and circadian disruption, understanding the mechanisms underlying glucose homeostasis regulation by the circadian clock and its dysregulation may improve glycemic control. In this review, we summarize the current knowledge on the tight interconnection between the timekeeping system, glucose homeostasis, and insulin sensitivity. We focus specifically on the involvement of astrocyte clocks, at the organism, cellular, and molecular levels, in the regulation of glucose metabolism.

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.

scholarly journals Exercising for Insulin Sensitivity – Is There a Mechanistic Relationship With Quantitative Changes in Skeletal Muscle Mass?

2021 ◽  
Vol 12 ◽  
Author(s):  
Jasmine Paquin ◽  
Jean-Christophe Lagacé ◽  
Martin Brochu ◽  
Isabelle J. Dionne
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Metabolic Health ◽  
Whole Body ◽  
Future Research ◽  
Level Of Evidence ◽  
Exercise Interventions ◽  
Quantitative Changes ◽  
The Impact

Skeletal muscle (SM) tissue has been repetitively shown to play a major role in whole-body glucose homeostasis and overall metabolic health. Hence, SM hypertrophy through resistance training (RT) has been suggested to be favorable to glucose homeostasis in different populations, from young healthy to type 2 diabetic (T2D) individuals. While RT has been shown to contribute to improved metabolic health, including insulin sensitivity surrogates, in multiple studies, a universal understanding of a mechanistic explanation is currently lacking. Furthermore, exercised-improved glucose homeostasis and quantitative changes of SM mass have been hypothesized to be concurrent but not necessarily causally associated. With a straightforward focus on exercise interventions, this narrative review aims to highlight the current level of evidence of the impact of SM hypertrophy on glucose homeostasis, as well various mechanisms that are likely to explain those effects. These mechanistic insights could provide a strengthened rationale for future research assessing alternative RT strategies to the current classical modalities, such as low-load, high repetition RT or high-volume circuit-style RT, in metabolically impaired populations.

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 Activin B regulates islet composition and islet mass but not whole body glucose homeostasis or insulin sensitivity

2012 ◽  
Vol 303 (5) ◽  
pp. E587-E596 ◽  
Author(s):  
Lara Bonomi ◽  
Melissa Brown ◽  
Nathan Ungerleider ◽  
Meghan Muse ◽  
Martin M. Matzuk ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Homeostasis ◽  
Activin A ◽  
Whole Body ◽  
Null Mouse ◽  
Islet Function ◽  
Islet Mass ◽  
Glucose Stimulated Insulin Secretion

Based on the phenotype of the activin-like kinase-7 (ALK7)-null mouse, activins A and B have been proposed to play distinct roles in regulating pancreatic islet function and glucose homeostasis, with activin A acting to enhance islet function and insulin release while activin B antagonizes these actions. We therefore hypothesized that islets from activin B-null (BBKO) mice would have enhanced glucose-stimulated insulin secretion. In addition, we hypothesized that this enhanced islet function would translate into increased whole body glucose tolerance. We tested these hypotheses by analyzing glucose homeostasis, insulin secretion, and islet function in BBKO mice. No differences were observed in fasting glucose or insulin levels, glucose tolerance, or insulin sensitivity compared with weight-matched young or older males. Similarly, there were no significant differences in insulin secretion comparing islets from WT or BBKO males at either age. However, BBKO islets were more sensitive to activin A, myostatin (MSTN), and follistatin (FST) treatments, so that activin A and FST inhibited and MSTN enhanced glucose stimulated insulin secretion. While mean islet area and the distribution of islet areas were not different between the genotypes, islet mass, islet number, and the proportion of α-cells/islet were significantly reduced in BBKO islets. These results indicate that activin B does not antagonize activin A to influence whole body glucose homeostasis or β-cell function but does influence islet mass and proportion of α-cells/islet. Therefore, loss of activin B signaling alone does not account for the ALK7-null phenotype, but activin B may have important roles in modulating islet mass, islet number, and the cellular composition of islets.

scholarly journals Galectin-3 gene deletion results in defective adipose tissue maturation and impaired insulin sensitivity and glucose homeostasis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Claudia Blasetti Fantauzzi ◽  
Carla Iacobini ◽  
Stefano Menini ◽  
Martina Vitale ◽  
Gian Pio Sorice ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Cell Function ◽  
Whole Body ◽  
Metabolic Derangement ◽  
Abnormal Glucose Regulation ◽  
Galectin 3 ◽  
Β Cell Function

AbstractAdiposopathy is a pathological adipose tissue (AT) response to overfeeding characterized by reduced AT expandability due to impaired adipogenesis, which favors inflammation, insulin resistance (IR), and abnormal glucose regulation. However, it is unclear whether defective adipogenesis causes metabolic derangement also independently of an increased demand for fat storage. As galectin-3 has been implicated in both adipocyte differentiation and glucose homeostasis, we tested this hypothesis in galectin-3 knockout (Lgal3−/−) mice fed a standard chow. In vitro, Lgal3−/− adipocyte precursors showed impaired terminal differentiation (maturation). Two-month-old Lgal3−/− mice showed impaired AT maturation, with reduced adipocyte size and expression of adipogenic genes, but unchanged fat mass and no sign of adipocyte degeneration/death or ectopic fat accumulation. AT immaturity was associated with AT and whole-body inflammation and IR, glucose intolerance, and hyperglycemia. Five-month-old Lgal3−/− mice exhibited a more mature AT phenotype, with no difference in insulin sensitivity and expression of inflammatory cytokines versus WT animals, though abnormal glucose homeostasis persisted and was associated with reduced β-cell function. These data show that adipogenesis capacity per se affects AT function, insulin sensitivity, and glucose homeostasis independently of increased fat intake, accumulation and redistribution, thus uncovering a direct link between defective adipogenesis, IR and susceptibility to diabetes.

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