Skip to main page content
U.S. flag
See More

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jul;18(7):1123-1138.
doi: 10.15252/embr.201643827. Epub 2017 May 24.

Mfn2 deletion in brown adipose tissue protects from insulin resistance and impairs thermogenesis

Kiana Mahdaviani  1   2 , Ilan Y Benador  1   2 , Shi Su  1 , Raffi A Gharakhanian  1 , Linsey Stiles  1   2 , Kyle M Trudeau  1   2 , Maria Cardamone  3 , Violeta Enríquez-Zarralanga  1 , Eleni Ritou  1   2 , Tamar Aprahamian  4 , Marcus F Oliveira  1   5 , Barbara E Corkey  1 , Valentina Perissi  3 , Marc Liesa  6   2 , Orian S Shirihai  6   2   7
Affiliations

Mfn2 deletion in brown adipose tissue protects from insulin resistance and impairs thermogenesis

Kiana Mahdaviani et al. EMBO Rep. 2017 Jul.

Abstract

BAT-controlled thermogenic activity is thought to be required for its capacity to prevent the development of insulin resistance. This hypothesis predicts that mediators of thermogenesis may help prevent diet-induced insulin resistance. We report that the mitochondrial fusion protein Mitofusin 2 (Mfn2) in BAT is essential for cold-stimulated thermogenesis, but promotes insulin resistance in obese mice. Mfn2 deletion in mice through Ucp1-cre (BAT-Mfn2-KO) causes BAT lipohypertrophy and cold intolerance. Surprisingly however, deletion of Mfn2 in mice fed a high fat diet (HFD) results in improved insulin sensitivity and resistance to obesity, while impaired cold-stimulated thermogenesis is maintained. Improvement in insulin sensitivity is associated with a gender-specific remodeling of BAT mitochondrial function. In females, BAT mitochondria increase their efficiency for ATP-synthesizing fat oxidation, whereas in BAT from males, complex I-driven respiration is decreased and glycolytic capacity is increased. Thus, BAT adaptation to obesity is regulated by Mfn2 and with BAT-Mfn2 absent, BAT contribution to prevention of insulin resistance is independent and inversely correlated to whole-body cold-stimulated thermogenesis.

Keywords: Mitofusin 2; brown adipose tissue; insulin resistance; obesity; thermogenesis.

PubMed Disclaimer

Figures

Figure EV1
Figure EV1. Diet‐induced obesity increases Mfn2 and mitochondrial respiratory capacity in BAT
  1. A

    Representative Western blot measuring Mfn2, Tomm20, and Porin on BAT total lysates from wild type female mice fed a chow diet or a high fat diet (HFD).

  2. B

    Protein level quantification of Tomm20 and Porin per microgram of protein loaded, as well as Mfn2 protein levels normalized to their corresponding loading control (Tomm20). Bars represent average of Tomm20, Porin, and Mfn2/Tomm20 from n = 3–8 female mice per group ± SEM.

  3. C

    Quantification of mitochondrial DNA (mtDNA) normalized to nuclear DNA (nDNA) by qPCR on extracted DNA from BAT of wild type female mice fed a chow diet or a HFD at 22°C or 30°C. Bars represent average of mDNA/nDNA from n = 3 female mice per group ± SEM.

  4. D

    Representative EM images of BAT extracted from wild type female mice fed a chow diet or a high fat diet (HFD).

  5. E

    Representative Western blot measuring complex I subunit Ndufb8, complex II Sdhb, complex III Uqcrc2, complex IV Cox1, and outer mitochondrial membrane Tomm20 in BAT total lysates from wild type female mice fed a chow or HFD.

  6. F

    Protein level quantification of the four complex subunits normalized by corresponding Tomm20 levels. Bar graphs represent average ± SEM of complexes normalized to Tomm20 from n = 5–8 female mice per group fed a chow diet or a HFD.

  7. G

    Representative Western blot measuring uncoupling protein 1 (Ucp1) and outer mitochondrial membrane Porin in BAT total lysates from wild type female mice fed a chow or HFD.

  8. H

    Protein level quantification of Ucp1 and the corresponding loading control Porin levels. Bar graphs represent average ± SEM of Ucp1 normalized to Porin from n = 5–8 wild type female mice per group fed a chow diet or a HFD.

  9. I–K

    Quantification of oxygen consumption rates (OCR) in BAT isolated mitochondria from wild type female mice fed a chow diet or a HFD under the different respiratory states. State 2 quantifies respiration driven by proton leak (no‐ATP synthesis), state 3 quantifies respiration linked to maximal ATP synthesis, and maximal represents maximal electron transport chain activity induced by FCCP. Bar graphs represent average ± SEM for complex I‐driven respiration (pyruvate + malate, n = 4–8 mice per group) (I), complex II‐driven respiration (succinate−rotenone, n = 4–8 mice per group) (J), and fatty acid oxidation (palmitoyl carnitine−malate, n = 3–6 mice per group) (K).

  10. L–N

    Quantification of OCR in BAT isolated mitochondria from wild type male mice fed a chow diet or a HFD under the different respiratory states. State 2 quantifies respiration driven by proton leak (no‐ATP synthesis), state 3 quantifies respiration linked to maximal ATP synthesis, and maximal represents maximal electron transport chain activity induced by FCCP. Bar graphs represent average ± SEM for complex I‐driven respiration (pyruvate + malate, n = 3–13 mice per group) (L), complex II‐driven respiration (succinate−rotenone, n = 3–13 mice per group) (M), and fatty acid oxidation (palmitoyl carnitine‐malate, n = 2 mice per group).

  11. O

    Mouse body temperature measurements from n = 5–11 wild type female mice per group at 9 months old and fed a chow diet, a high fat diet (HFD) either at 22°C or at thermoneutrality 30°C. Values shown are means ± SEM.

Data information: Statistical analysis: * represents significance using Student's t‐test, unpaired P < 0.05.
Figure 1
Figure 1. Mfn2 deletion in BAT results in cold intolerance and BAT lipohypertrophy

  1. Representative Western blot measuring Mfn2 and Ucp1 in total lysates from different tissues of BAT‐Mfn2‐KO (KO) male mice. WAT S, subcutaneous white adipose tissue; WAT G, perigonadal white adipose tissue. Soleus muscle (S), Gastrocnemius muscle (G).

  2. Body temperature measurements before and during cold exposure (4°C) of n = 7–9 control and BAT‐Mfn2‐KO female mice per group at 9 months old and fed a chow diet. Values shown are means ± SEM. * represents significance using two‐way ANOVA test WT vs. KO, P < 0.05.

  3. Body temperature measurements before and during cold exposure (4°C) of n = 13–19 control and BAT‐Mfn2‐KO male mice per group at 9 months old and fed a chow diet. Values shown are means ± SEM. * represents significance using two‐way ANOVA test WT vs. KO, P < 0.05.

  4. Representative Western blot measuring Ucp1 and Tomm20 (mitochondrial loading control) in BAT total lysates from control (WT) and BAT‐Mfn2‐KO (KO) female mice.

  5. Protein level quantification of Tomm20 and Ucp1 levels per microgram of protein loaded. Bars represent average of Tomm20 and Ucp1 levels from n = 4–5 mice per group ± SEM. * represents significance using Student's t‐test, unpaired P < 0.05.

  6. Body weight measurements of n = 7–9 control and BAT‐Mfn2‐KO female mice per group under chow diet over 38 weeks. Values shown are average ± SEM. Two‐way ANOVA test, P > 0.05.

  7. Body weight measurements of n = 13–19 control and BAT‐Mfn2‐KO male mice per group under chow diet over 38 weeks. Values shown are average ± SEM. Two‐way ANOVA test, P > 0.05.

  8. Quantification of the various WAT and BAT depot weights of n = 4–6 control (WT) and BAT‐Mfn2‐KO (KO) female mice (14–15 months old) per group on chow diet. Bar graphs represent average ± SEM. * represents significance using Student's t‐test, unpaired, P < 0.05.

  9. Quantification of the various WAT and BAT depot weights of n = 13–19 control (WT) and BAT‐Mfn2‐KO (KO) male mice (14–15 months old) per group on chow diet. Bar graphs represent average ± SEM. * represents significance using Student's t‐test, unpaired, P < 0.05.

  10. Representative images of H&E staining of the BAT sections isolated from control (WT) and BAT‐Mfn2‐KO (KO) female and male mice.

  11. Quantification of the brown adipocyte cell size (n = 15–25 cells) and lipid droplet size (n = 124–250 lipid droplets) from the BAT isolated from n = 3–5 control (WT) and BAT‐Mfn2‐KO (KO) male mice per group. Values shown are average ± SEM and are expressed as arbitrary units. * represents significance using Student's t‐test, unpaired P < 0.05.

Figure EV2
Figure EV2. BAT‐Mfn2‐KO male mice are protected from HFD‐induced insulin resistance and increase BAT glycolytic capacity, despite showing the same body fat gain and being cold‐intolerant

  1. Body composition of n = 8–9 wild type (WT) and BAT‐Mfn2‐KO (KO) male mice (7 months) per group on chow diet. Bar graph represent average of % fat and % lean mass of total body weight ± SEM.

  2. Body composition of n = 4–6 wild type (WT) and BAT‐Mfn2‐KO (KO) male mice (7 months) per group on a HFD at ambient temperature (22°C). Bar graph represent average of % fat and % lean mass of total body weight ± SEM.

  3. Glucose tolerance test (GTT) on n = 11–16 wild type (WT) and BAT‐Mfn2‐KO (KO) male mice per group at 5 months old, fed chow diet. Values shown are average ± SEM.

  4. GTT on n = 10–13 wild type (WT) and BAT‐Mfn2‐KO (KO) male mice per group, fed a HFD at 22°C. Values shown are average ± SEM. Two‐way ANOVA test, WT vs. KO, P < 0.05.

  5. Body weight measurements of n = 8–9 wild type (WT) and BAT‐Mfn2‐KO (KO) male mice per group on HFD at an ambient temperature of 22°C (room temperature, RT) over 40 weeks. Values shown are average ± SEM. Two‐way ANOVA test, WT vs. KO, *P < 0.05.

  6. Quantification of WAT and BAT deposit weight isolated from n = 4–6 wild type (WT) and BAT‐Mfn2‐KO (KO) male mice per group fed a HFD at ambient temperature (22°C). Bar graphs represent average ± SEM. * represents significance using Student's t‐test, unpaired P < 0.05.

  7. Insulin tolerance tests (ITT) on n = 9–13 wild type (WT) and BAT‐Mfn2‐KO (KO) male mice per group, fed a HFD at ambient temperature (22°C). Values shown are average ± SEM. Two‐way ANOVA test, WT vs. KO, *P < 0.05.

  8. Body temperature measurements of wild type (WT) and BAT‐Mfn2‐KO (KO) male (n = 10–12) mice at 9 months old in HFD groups at ambient temperature. Values shown in both panels are means ± SEM. * represents significance using two‐way ANOVA test, WT vs. KO, P < 0.05.

  9. Representative Western blot measuring PGAM1, PKM2, and HSP90 in BAT total lysates from wild type (WT) and BAT‐Mfn2 KO (KO) males on HFD.

  10. Protein level quantification of PGAM1 and PKM2 normalized by HSP90 level, used as loading control. Bar graphs represent average ± SEM of proteins normalized to HSP90 from n = 3–4 mice per group of wild type (WT) and BAT‐Mfn2‐KO (KO) male mice. * represents significance using Student's t‐test, unpaired P < 0.05.

  11. Quantification of serum lactate from n = 3–6 male and n = 4–8 female mice per group of wild type (WT) and BAT‐Mfn2‐KO (KO) mice. Bar graphs represent average ± SEM of serum lactate (mM). # represents significance between male KO and female KO groups using Student's t‐test, unpaired P < 0.05.

Figure 2
Figure 2. BAT mitochondria from BAT‐Mfn2‐KO mice show improved respiratory capacity and changes in respiratory complex expression levels
  1. A–C

    Quantification of oxygen consumption rates (OCR) in BAT isolated mitochondria from wild type (WT) and BAT‐Mfn2‐KO female mice under chow diet under the different respiratory states. State 2 quantifies respiration driven by proton leak (no‐ATP synthesis), state 3 quantifies respiration linked to maximal ATP synthesis, and maximal represents maximal electron transport chain activity induced by FCCP. Bar graphs represent average ± SEM for complex I‐driven respiration (pyruvate–malate, n = 4–5 mice per group) (A), complex II‐driven respiration (succinate−rotenone, n = 4–5 mice per group) (B), and fatty acid oxidation (palmitoyl carnitine−malate, n = 3 mice per group) (C). * represents significance using Student's t‐test, unpaired P < 0.05.

  2. D–F

    Quantification of OCR in BAT isolated mitochondria from wild type (WT) and BAT‐Mfn2‐KO male mice under chow diet under the different respiratory states. State 2 quantifies respiration driven by proton leak (no‐ATP synthesis), state 3 quantifies respiration linked to maximal ATP synthesis, and maximal represents maximal electron transport chain activity induced by FCCP. Bar graphs represent average ± SEM for complex I‐driven respiration (pyruvate–malate, n = 13–19 mice per group) (D), complex II‐driven respiration (succinate−rotenone, n = 13–19 mice per group) (E), and fatty acid oxidation (palmitoyl carnitine−malate, n = 2–8 mice per group) (F). * represents significance using Student's t‐test, unpaired P < 0.05.

  3. G

    Respiratory complex expression levels: Representative Western blot measuring complex I subunit Ndufb8, complex II Sdhb, complex III Uqcrc2, complex IV Cox1, complex V Atp5a, and outer mitochondrial membrane protein Tomm20 in BAT total lysate from wild type (WT) and BAT‐Mfn2‐KO female mice.

  4. H

    Quantification of the five complex subunits normalized by Tomm20 level measured as shown in (G). Bar graphs represent average ± SEM of Tomm20 expression values and complexes normalized to Tomm20 from n = 5–7 mice per group of wild type (WT) and BAT‐Mfn2‐KO female mice. * represents significance using Student's t‐test, unpaired P < 0.05.

  5. I

    Oxygen consumption measurements in WT and BAT‐Mfn2‐KO anesthetized females under a chow diet 30 min after injection with the β3‐agonist CL‐316,243 (1 mg/kg). Bars represent average ± SEM of VO2 (ml/kg/min) consumed n = 4–7 mice per group.

Figure 3
Figure 3. BAT‐specific deletion of Mfn2 in females protects from diet‐induced obesity, despite cold intolerance

  1. Body weight measurements of n = 8–10 wild type (WT) and BAT‐Mfn2‐KO (KO) female mice per group on HFD at an ambient temperature of 22°C (room temperature, RT) over 40 weeks. Values shown are average ± SEM. Two‐way ANOVA test, WT vs. KO,* P < 0.05.

  2. Quantification of WAT and BAT depots weight isolated from n = 4–8 wild type (WT) and BAT‐Mfn2‐KO (KO) female mice per group fed a HFD at ambient temperature (22°C). Bar graphs represent average ± SEM. * represents significance using Student's t‐test, unpaired P < 0.05.

  3. Body weight measurements of n = 5–7 wild type (WT) and BAT‐Mfn2‐KO (KO) female mice per group fed a HFD at thermoneutrality (30°C) over 30 weeks. Values shown are average ± SEM. No significant differences detected. Two‐way ANOVA test, WT vs. KO.

  4. Quantification of WAT and BAT depots weight of n = 5–7 wild type (WT) and BAT‐Mfn2‐KO (KO) female mice per group fed a HFD at thermoneutrality (30°C). Bar graphs represent average ± SEM. * represents significance using Student's t‐test, unpaired P < 0.05.

  5. Quantification of the lipid droplet integrated density from the BAT isolated from wild type (WT) and BAT‐Mfn2‐KO (KO) female mice fed a chow diet (n = 5) or a HFD at either 22°C (n = 5–6) or 30°C (n = 4–8). Values shown are average ± SEM. * represents significance WT vs. KO using Student's t‐test, unpaired P < 0.05. # represents significance WT chow diet vs. WT HFD 30°C using Student's t‐test, unpaired P < 0.05.

  6. Representative Western blot measuring Ucp1 and GAPDH (mitochondrial loading control) in BAT total lysates from wild type (WT) and BAT‐Mfn2‐KO (KO) female mice fed a HFD at 22°C or at 30°C.

  7. Protein level quantification of Ucp1 protein levels normalized to GAPDH. Bars represent average of Ucp1/GAPDH from n = 3–4 mice per group ± SEM. # represents significance using Student's t‐test, unpaired HFD 22°C vs. 30°C P < 0.05.

  8. Body temperature measurements before and during cold exposure (4°C) of wild type (WT) and BAT‐Mfn2‐KO (KO) female (n = 7–11 mice per group), at 9 months old, fed a HFD at ambient temperature. Values shown in both panels are means ± SEM. * represents significance using two‐way ANOVA test, WT vs. KO, P < 0.05.

  9. Body temperature measurements before and during cold exposure (4°C) of wild type (WT) and BAT‐Mfn2‐KO (KO) female mice (n = 5–7 mice per group), at 9 months old, fed a HFD at thermoneutral temperature. Values shown in both panels are means ± SEM. * represents significance using two‐way ANOVA test, WT vs. KO, P < 0.05. Red dotted line: At this time point all the KO mice were removed from the cold room due to severe cold intolerance.

Figure 4
Figure 4. BAT‐specific deletion of Mfn2 prevents HFD‐induced insulin resistance

  1. Glucose tolerance test (GTT) on n = 5–7 wild type (WT) and BAT‐Mfn2‐KO (KO) female mice per group at 5 months old, fed chow diet.

  2. GTT on n = 10 wild type (WT) and BAT‐Mfn2‐KO (KO) female mice per group, fed a HFD at 22°C.

  3. GTT on n = 5–7 wild type (WT) and BAT‐Mfn2‐KO (KO) female mice per group, fed a HFD at thermoneutral temperature (30°C).

  4. Insulin tolerance tests (ITT) on n = 8–10 wild type (WT) and BAT‐Mfn2‐KO (KO) female mice per group, fed a HFD at 22°C.

  5. ITT on n = 5–7 wild type (WT) and BAT‐Mfn2‐KO (KO) female mice per group, fed a HFD at thermoneutral temperature (30°C). Glucose injection was required due to hypoglycemia 60 min after insulin injection to some BAT‐Mfn2‐KO mice.

  6. Representative images of H&E staining of the liver sections isolated from wild type (WT) and BAT‐Mfn2‐KO (KO) female mice, fed a HFD at thermoneutrality (30°C).

  7. Quantification of the integrated density of lipid droplet signal in liver sections from n = 5–6 wild type (WT) and BAT‐Mfn2‐KO (KO) female mice per group fed a HFD at thermoneutrality. Each dot represents a mouse and values shown are expressed as arbitrary units. Values shown are average ± SEM. Student's t‐test, unpaired P > 0.05.

  8. Quantification of the integrated density of lipid droplet signal in liver sections from n = 4–8 wild type (WT) and BAT‐Mfn2‐KO (KO) female mice per group fed a HFD at 22°C. Each dot represents a mouse and values shown are expressed as arbitrary units. Values shown are average ± SEM. Student's t‐test, unpaired P > 0.05.

Data information: Values in panels (A–E) are average ± SEM. * represents significance using two‐way ANOVA test, P < 0.05.
Figure 5
Figure 5. Mfn2 deletion increases the efficiency of ATP synthesizing respiration of BAT mitochondria oxidizing fat in obese females, but not in males
  1. A

    Representative Western blot analysis measuring complex I subunit Ndufb8, complex II Sdhb, complex III Uqcrc2, complex IV Cox1, complex V Atp5a, and outer mitochondrial membrane Tomm20 in BAT total lysate from wild type (WT) and BAT‐Mfn2 KO (KO) female mice on high fat diet (HFD).

  2. B

    Protein level quantification of Tomm20 per microgram of total protein loaded, and the five complex subunits normalized by Tomm20 level, used as loading control. Bar graphs represent average ± SEM of Tomm20 expression values and complexes normalized to Tomm20 from n = 4–8 mice per group of wild type (WT) and BAT‐Mfn2‐KO (KO) female mice. * represents significance using Student's t‐test, unpaired P < 0.05.

  3. C–E

    Quantification of oxygen consumption rates (OCR) in BAT isolated mitochondria from wild type (WT) and BAT‐Mfn2‐KO (KO) female mice fed a HFD at room temperature 22°C. State 2 quantifies respiration driven by proton leak (no‐ATP synthesis), state 3 quantifies respiration linked to maximal ATP synthesis, and maximal represents maximal electron transport chain activity induced by FCCP. Bar graphs represent average ± SEM for complex I‐driven respiration (pyruvate–malate, n = 4–8 mice per group) (C), (succinate−rotenone, n = 4–8 mice per group) (D), and fatty acid oxidation (palmitoyl carnitine−malate, n = 4–6 mice per group) (E). * represents significance using Student's t‐test, unpaired P < 0.05.

  4. F

    Quantification of the respiratory control ratio (RCR, state 3/state 2) measured in isolated BAT mitochondria from n = 4–6 wild type (WT) and BAT‐Mfn2‐KO female mice per group fed a high fat diet at 22°C and using fatty acids (palmitoyl carnitine−malate) as fuels for oxidation. Bar graphs represent average ± SEM. * represents Student's t‐test, unpaired WT vs. KO P < 0.05.

  5. G–I

    Quantification of OCR in BAT isolated mitochondria from wild type (WT) and BAT‐Mfn2‐KO male mice fed a HFD at room temperature 22°C. State 2 quantifies respiration driven by proton leak (no‐ATP synthesis), state 3 quantifies respiration linked to maximal ATP synthesis, and maximal represents maximal electron transport chain activity induced by FCCP. Bar graphs represent average ± SEM for complex I‐driven respiration (pyruvate–malate, n = 3–6 mice per group) (G), (succinate−rotenone, n = 3–6 mice per group) (H), and fatty acid oxidation (palmitoyl carnitine−malate, n = 2–5 mice per group) (I). * represents significance using Student's t‐test, unpaired P < 0.05.

  6. J

    Quantification of the respiratory control ratio (RCR, state 3/state 2) measured in isolated BAT mitochondria from n = 2–5 wild type (WT) and BAT‐Mfn2‐KO (KO) male mice per group fed a HFD at 22°C and using fatty acids (palmitoyl carnitine−malate) as fuels for oxidation. Bar graphs represent average ± SEM. * represents Student's t‐test, unpaired WT vs. KO P < 0.05.

Figure 6
Figure 6. Increased capacity for fatty acids oxidation, coupled respiration and lipid import, accompanied by reduced serum lipids, in obese BAT‐Mfn2‐KO female mice
  1. A

    Quantification of the RER measurements at both light and dark cycles for n = 4–6 wild type (WT) and BAT‐Mfn2‐KO (KO) female mice per group fed a HFD at thermoneutrality (30°C). Values are calculated as the ratio of VCO2 to VO2 produced and consumed by the mice, respectively. Each dot represents a mouse. Values shown are average ± SEM. * represents significance using Student's t‐test, unpaired P < 0.05.

  2. B, C

    Metabolic efficiency of wild‐type (WT) and BAT‐Mfn2‐KO (KO) female mice fed a HFD at room temperature, 22°C (n = 10–11 mice per group) (B) and at thermoneutrality (n = 5–7 mice per group) (C). Values are calculated as gram of body weight gained per Kcal of energy intake. Values shown in both panels are mean ± SEM. * represents significance using Student's t‐test, unpaired P < 0.05.

  3. D

    Quantifications of mice whole‐body energy expenditure indicated as Kcal/24 h/mouse for n = 4–6 control and BAT‐Mfn2‐KO female mice per group under HFD at thermoneutrality (30°C), and multiple regression analysis of energy expenditure correlated to lean body mass for the same control and BAT‐Mfn2‐KO female mice under HFD at 9 months old in light and dark cycles. Each dot represents a mouse in all panels. Values shown are average ± SEM. Student's t‐test unpaired and ANCOVA test were used respectively.

  4. E

    Representative Western blot measuring lipoprotein lipase (LPL), CD36, and GAPDH on BAT total lysates from wild type (WT) and BAT‐Mfn2‐KO (KO) female mice fed a high fat diet (HFD) at 22°C.

  5. F

    Protein level quantification of LPL and CD36 protein levels normalized to their corresponding loading control (GAPDH). Bars represent average of LPL/GAPDH from n = 3–8 female mice per group ± SEM. * represents Student's t‐test, unpaired WT vs. KO P < 0.05.

  6. G

    Representative Western blot measuring LPL, CD36, and GAPDH on BAT total lysates from wild type (WT) and BAT‐Mfn2‐KO (KO) female mice fed a high fat diet (HFD) at 30°C.

  7. H

    Protein level quantification of LPL and CD36 protein levels normalized to their corresponding loading control (GAPDH). Bars represent average of LPL/GAPDH from n = 5–7 female mice per group ± SEM. * represents Student's t‐test, unpaired WT vs. KO P < 0.05.

  8. I

    Quantification of serum cholesterol levels of wild type (WT) and BAT‐Mfn2‐KO (KO) female mice fed a chow (n = 7 per group) or a high fat diet at 22°C (n = 7–11 per group) or 30°C (n = 4–7 per group). Bars represent average of serum cholesterol levels (mg/dL) ± SEM. * and # represent Student's t‐test, unpaired WT vs. KO (*) and HFD 22°C or HFD 30°C vs. chow diet (#) P < 0.05.

  9. J

    Quantification of serum triglyceride (TG) levels of wild type (WT) and BAT‐Mfn2‐KO (KO) female mice fed a high fat diet at 22°C (n = 7–11 per group) or 30°C (n = 5–7 per group). Bars represent average of serum TG levels (mg/dL) ± SEM. # represents Student's t‐test, unpaired HFD 22°C vs. HFD 30°C P < 0.05.

See this image and copyright information in PMC

Comment in

References

    1. Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84: 277–359 - PubMed
    1. Nicholls DG, Bernson VS, Heaton GM (1978) The identification of the component in the inner membrane of brown adipose tissue mitochondria responsible for regulating energy dissipation. Experientia Suppl 32: 89–93 - PubMed
    1. Nicholls DG (2001) A history of UCP1. Biochem Soc Trans 29: 751–755 - PubMed
    1. Shimizu I, Aprahamian T, Kikuchi R, Shimizu A, Papanicolaou KN, MacLauchlan S, Maruyama S, Walsh K (2014) Vascular rarefaction mediates whitening of brown fat in obesity. J Clin Invest 124: 2099–2112 - PMC - PubMed
    1. Duteil D, Tosic M, Lausecker F, Nenseth HZ, Muller JM, Urban S, Willmann D, Petroll K, Messaddeq N, Arrigoni L et al (2016) Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue. Cell Rep 17: 1008–1021 - PMC - PubMed

Publication types