FTO contributes to the development of hyperglycaemia.

<p>All data are elevated from female mice. *indicate significant p-values between <i>Lep^ob/ob;Fto^+/+</i>and <i>Lep^ob/ob;Fto^−/−</i>. a) Fasted glucose levels in mice at the age of 6 weeks (n = 13, 10, 12, 8) b) Non-fasted glucose level at the age of 7 weeks (n = 12, 9, 12, 9). c) Glucose tolerance test (GTT) at the age of 6 weeks (n = 13, 10, 12, 8). d) Insulin tolerance test (ITT) at the age of 7 weeks (n = 12, 9, 12, 9). Glucose values are presented relative to initial glucose levels. e) Fasted glucose levels in mice at the age of 14 weeks (n = 11, 7, 9, 9). f) Non-fasted glucose level at the age of 15 weeks (n = 11, 8, 14, 12). g) GTT at the age of 14 weeks (n = 11, 7, 9, 9). h) ITT at the age of 15 weeks (n = 11, 8, 14, 12). Glucose values are presented relative to initial glucose levels. i) Plasma glucose levels of 30 weeks old non fasted mice (n = 8, 5, 5, 6). j) Plasma insulin levels of non-fasted mice at the age of 30 weeks (n = 3, 3, 7, 3). All data are presented as mean. Error bars indicate the SEM.</p

Detailed analysis of adipose tissue.

<p>All data are collected from 30 weeks old mice. *indicate significant p-values between <i>Lep^ob/ob;Fto^+/+</i> and <i>Lep^ob/ob; Fto^−/−</i>. a) Weights of different fat pads from female mice (n = 13, 16, 18, 16). b) Area size of epigonadal fat cells from female mice (n = 4, 4, 8, 7). c+d) Expression analysis for different marker genes of epigonadal adipose tissue (n = 6, 4, 5, 5, 5). Following p-values were calculated: between <i>Lep^ob/ob;Fto^+/−</i> and <i>Lep^ob/ob; Fto^−/−</i>: PPARγ2: p = 0,08, Adiponectin: p = 0,21, TNFα:p = 0,06, IL-6:p = 0,03. Data are presented as mean. Error bars indicate the SEM.</p

FTO contributes to gain of body weight in <i>Lep^ob/ob</i> mice.

<p>All data are collected from female mice. a) Development of body weight from 3 to 16 weeks of age. n(<i>Lep^+/+; Fto^+/+</i>) = 15–20, n(<i>Lep^ob/ob;Fto^+/+</i>) = 11–13, n(<i>Lep^ob/ob;Fto^+/−</i>) = 15–19, n(<i>Lep^ob/ob;Fto^−/−</i>) = 9–12, n(<i>Lep^+/+;Fto^−/−</i>) = 4–6. Asterisks (*) indicate significant p-values between <i>Lep^ob/ob;Fto^−/−</i> and <i>Lep^ob/ob;Fto^+/+</i>. Further significant p-values were found: <i>Lep^+/+;Fto^+/+</i>–<i>Lep^ob/ob;Fto^−/−</i>: p≤0,05 (weeks 3–8+11–16); <i>Lep^+/+;Fto^+/+</i>–<i>Lep^ob/ob;Fto^+/+</i>: p≤0,05 (weeks 4–16); <i>Lep^+/+;Fto^+/+</i>–<i>Lep^ob/ob;Fto^+/−</i>: p≤0,05 (weeks 4–16); <i>Lep^ob/ob;Fto^−/−</i>–<i>Lep^ob/ob;Fto^+/−</i>: p≤0,05 (weeks 3–16); <i>Lep^ob/ob;Fto^+/+</i>–<i>Lep^ob/ob;Fto^+/−</i>: p≤0,05 (weeks 4–14);; <i>Lep^+/+;Fto^+/+</i>–<i>Lep^+/+;Fto^−/−</i>: p≤0,05 (weeks 3–16). b–e) *indicate significant p-values to <i>Lep^ob/ob;Fto^+/+</i>. b) Body length at the age of 30 weeks (n = 14, 15, 17, 15, 10). c) Body weight in relation to body length at the age of 9 (n = 6, 6, 7, 5, 5), 16 weeks (n = 4, 6, 7, 5, 4) and 30 weeks (n = 14, 15, 17, 15, 10) of age. d) Lean mass and fat mass at the age of 8 weeks (n = 7, 8, 4, 4, 3). e) Lean mass and fat mass at the age of 16 weeks (n = 12, 7, 9, 4, 3). All data are presented as mean. Error bars indicate the SEM.</p

Accumulation of fat in liver of leptin-deficient mice is influenced by FTO.

<p>a) Liver weight in relation to body length (n = 13, 14, 16, 14). *indicate significant p-values between <i>Lep^ob/ob;Fto^+/+</i>and <i>Lep^ob/ob;Fto^−/−</i>. b) Haematoxylin and eosin staining on paraffin sections (upper row) and oil red O staining on cryo sections (lower row) for all 4 genotypes. Scale = 100 µm. Livers were used from female mice at the age of 30 weeks. All data are presented as mean. Error bars indicate the SEM.</p

Increase of pancreatic islet size in leptin-deficient mice is depending on FTO.

<p>a) Haematoxylin and eosin staining on paraffin sections of the pancreas for all 4 genotypes. b) Immunofluorescence staining for insulin (red) and glucagon (green) on pancreas sections. Nuclei are stained with DAPI. Scale = 100 µm. c) Area of beta cells in relation to full pancreas section area. d) Number of islets of Langerhans which were found on sections categorized into 3 groups of size. Pancreas were taken from 30 weeks old female mice (n = 5, 6, 7, 5). All data are presented as mean. Error bars indicate the SEM.</p