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  4. John-Olov Jansson

John-Olov Jansson

Senior Researcher

Department of Physiology
Telephone
+46 31-786 35 26
+46 739-01 11 22
Mail
john-olov.jansson@neuro.gu.se
Visiting address
Medicinaregatan 11-13
41390 Göteborg
Postal address
Box 432
40530 Göteborg

About John-Olov Jansson

Research group

The gravitostat - a novel system regulating body fat homeostasis

Teaching

Endocrinology for medical students and pharmacy students for more than 15 years. Since 2009 course leader for “BF2”, a course introducing scientific techniques and principles to medical students. The course was organised from scratch by JOJ.

Research project 1

The gravitostat - a novel system regulating body fat homeostasis

A recently started project describes a new mechanism for homeostatic regulation of fat mass, the gravitostat, which utilizes a sensor of axial loading in the lower extremities. Our findings demonstrate that the gravitostat regulates fat mass in obese mice while leptin regulates fat mass only in lean mice with low endogenous serum leptin levels (Ref 2, Endocrinology 2018). Interestingly, we now have evidence for gravitostat action also in obese humans (Ref 1, EClinicalMedicine 2020). We propose that activation of the primarily protects against obesity while low levels of leptin protects against undernutrition. This would mean that the gravitostat would be more likely than leptin to provide clinical treatment of obesity (Ref 4, PNAS 2018, Ref 2, Endocrinology 2018; Ref 1, EClinicalMedicine 2020).

Research project 2

Glucagon-like peptide-1 (GLP-1) suppresses body fat mass via interleukin-6 (IL-6) in the brain.

A long-term research aim for many years has been to study the interactions between the immune system and metabolic function. We were first to show that lack of biological effects of endogenous interleukin-6 (IL-6; Wallenius V et al 2002, Nat Med 8:75-79; over 1350 citations in Google Scholar) or IL-1 (Garcia M et al Diabetes 55:1205-1213; 122 citations), causes mature onset obesity in mice, probably by increasing energy expenditure at the level of the central nervous system. In 2013, we found that brainstem glucagon-like peptide-1 (GLP-1) exerts its clinically relevant anti-obesity effect by increasing the expression of IL-6 and IL-1, but not TNFa, in the brain (Shirazi R et al 2013, Proc Natl Acad Sci, USA 110: 16199-16204). This is a great interest since we have long-term interest in the metaolic of IL-6 and since GLP-1 analogues, such as exendin-4 (Byetta and Bydureon) and liraglutide (Victoza and Saxenda) are widely used for treatment of type 2 diabetes and obesity. Surprisingly little has been known about the mechanism of action of this important group of drugs. Our aim is to investigate how and where in the brain the chain of events occurs in which GLP-1 decreases obesity by increasing IL-6 (and IL-1).

Ten most important publications:

  1. Ohlsson C, Gidestrand E, Bellman J, Larsson C, Palsdottir V, Hägg D, Jansson PA, Jansson JO. 2020. Increased Weight Loading Reduces Body Weight and Body Fat in Obese Subjects – A proof of concept randomized clinical trial. EClinicalMedicine. (Lancet group) doi.org/10,1016/j_eclinm.2020.100338. Implicates that there is a gravitostat also in humans.
  2. Ohlsson C, Hägg DA, Hammarhjelm F, Dallmau Gasull A, Bellman J, Windahl S, Palsdottir V, Jansson JO. 2018. Endocrinology The gravitostat regulates fat mass in obese male mice while leptin regulates fat mass in lean male mice. Endocrinology, en.2018-00307, . (A possible reason that leptin is ineffective in the obese, could be that it is a fasting signal. Instead, the gravitostat is the physiological anti-obesity signal.)
  3. Ohlsson C, Jansson JO. 2018. Reply toLund: Where does the gravitostat fit in? Proc Natl Acad Sci U S A. 115:E1335. doi: 10.1073/pnas.1800116115.
  4. Jansson JO, Palsdottir V, Hägg DA, Schéle E, Dickson SL, Anesten F, Bake T, Montelius M, Bellman J, Johansson ME, Cone RD, Drucker DJ, Wu J, Aleksic B, Törnqvist AE, Sjögren K, Gustafsson JÅ, Windahl SH, Ohlsson C. 2018. Body weight homeostat that regulates fat mass independently of leptin in rats and mice. Proc Natl Acad SciU S A. 115:427-432. doi:10.1073/pnas.1715687114. PMID: 29279372. (Almost 25 years after leptin, we report another leptin independent homeostatic regulator of body fat; the gravitostat.)
  5. Anesten F, Santos C, Gidestrand E, Schéle E, Pálsdóttir V, Swedung-Wettervik T, Meister B, Patrycja Skibicka K, Jansson JO. 2017. Functional interleukin-6 receptor-α is located in tanycytes at the base of the third ventricle. J Neuroendocrinol. Vol 29. doi: 10.1111/jne.12546.
  6. Anesten F, Mishra D, Dalmau Gasull A, Bellman J, Palsdottir V, Zhang FP, Trapp S, Skibicka KP, Poutanen M, Jansson JO. 2019. GLP-1-, but not GDF-15-, receptor activation increases the number of IL-6-expressing cells in the external lateral parabrachial nucleus. Neuroendocrinology doi:10.1159/000499693, In line with article 6 that IL-6 mediates antiobesity effect by GLP-1
  7. Shirazi R, Palsdottir V, Collander J, Anesten F, Vogel H, Langlet F, Jaschke A, Schuermann A, Prevot V, Shao R,Jansson J-O (corresponding author), Skibicka KP. 2013. GLP-1 receptor stimulation induced suppression of food intake and body weight is mediated by central interleukin-1 and interleukin-6. Proc Natl Acad Sci, U S A, 110:16199-16204 (Proof that some of the most used metabolism drugs in the world act via IL-6 (and IL-1, but not TNFa).
  8. Garcia M, Wernstedt I, Berndtsson A, Enge M, Bell M, Hultgren O, Horn M, Ahren B, Enerbäck S, Ohlsson C, Wallenius V, Jansson J-O. 2006. Mature onset obesity in interleukin-1 receptor I (IL-1RI) knockout mice. Diabetes, 55:1205-1213. (The first article to show that endogenous IL-1 activation, like IL-6, but unlike TNFa, decreases fat mass in health. 153 citations)
  9. Wallenius V, Wallenius K, Ahrén B, Rudling M, Dickson SL, Ohlsson C, Jansson J-O. 2002 Interleukin-6 deficient mice develop mature-onset obesity. Nature Medicine 8:75-79. (The first article to show that endogenous IL-6, like IL-1 but unlike TNFa, decreases fat mass in health. 1350 citations in Google Scholar.)
  10. Jansson J O, Downs T R, Beamer W G, Frohman L A: 1986. Receptor associated resistance to growth hormone releasing factor in dwarf "little" mice. 91̽ 232:511 512. (In this article we show that dwarfism in the “little” mouse is due to a defective GHRH –receptor. This was confirmed in mice in 1993, and later seen in human dwarfs. 140 citations.)

Publications: In total 170, many of which in high impact journals like 91̽, Cell Metab, Nat Med, Nat Gen.

Citations: In total 26 000 citations H-index 70 (Googles Scholar), H-index 56 (Web of 91̽) August 2021).

Our article in Nat Med 2002 showing that endogenous interleukin-6 suppreses body fat mass has been cited over 1300 tines (Google Scholar).