Directory

Understanding why individuals differ in their ability to maintain metabolic balance under stress is an unsolved challenge in metabolic research. Such interindividual variation in physiological adaptation and energy homeostasis drives differences in disease susceptibility, progression, and treatment response. Yet these differences cannot be fully explained by inherited genetics, pointing to additional somatic and metabolic layers of regulation. 

My laboratory investigates how energetic inefficiency, particularly through futile metabolic cycles, enables cells and tissues to adapt and maintain homeostasis. We investigate if variation in futile cycle activity contributes to short-term, reversible metabolic flexibility, while somatic mutations in metabolic tissues provide a longer-term, cell-specific layer of adaptation. Together, these processes may underlie the unexplained diversity of metabolic phenotypes observed across individuals. 

Using mechanistic biochemistry, genetic perturbation, and single-cell and multi-omics analyses, we aim to dissect how futile lipid cycling modulates signaling and identify how somatic mosaicism reprograms metabolic circuits ((in)dependent of futile cycling). By quantitatively linking energetic inefficiency and somatic variation, our research will establish a new framework for understanding adaptive homeostasis, offering insights into metabolic resilience, disease heterogeneity, and opportunities for novel metabolic therapy modalities. 

Futile cycles: Emerging utility from apparent futility.

Cell metabolism – Sharma Anand Kumar*; Khandelwal Radhika; Wolfrum Christian* (2024)

36 (6); 1184-1203

DGAT-driven futile lipid cycling has a pronounced, yet concealed, thermogenic function.

Cell metabolism – Sharma Anand Kumar*; Khandelwal Radhika; Zurkovic Jelena; Long Fen; Wang Tongtong; Dewal Revati S; Wu Chunyan; Ghosh Adhideb; Manuel Klug; Othman Alaa; Chitraju Chandramohan; Farese Robert V; Walther Tobias C; Balaz Miroslav; Thiele Christoph; Wolfrum Christian* (2026)

38 (6); 1154-1171.e7

Futile lipid cycling: from biochemistry to physiology.

Nature metabolism – Sharma Anand Kumar*; Khandelwal Radhika; Wolfrum Christian* (2024)

6 (5); 808-824

Basal re-esterification finetunes mitochondrial fatty acid utilization.

Molecular metabolism – Sharma Anand Kumar; Wang Tongtong; Othman Alaa; Khandelwal Radhika; Balaz Miroslav; Modica Salvatore; Zamboni Nicola; Wolfrum Christian (2023)

71

Intricacies and obscurities of non-shivering thermogenesis.

Nature reviews. Endocrinology – Sharma Anand Kumar* (2025)

21 (1); 9-9

MEDAG functions as an A-kinase-anchoring protein in adipocytes.

Molecular cell – Long Fen; Ghosh Adhideb; Xu Tianyu; Ding Lianggong; Wu Chunyan; Khandelwal Radhika; Noé Falko; Sun Wenfei; Dong Hua; Wang Tongtong; Hoffmann Anne; Gardeux Vincent; Deplancke Bart; Abu-Nawwas Laith; Stefanicka Patrik; Varga Lukas; Ruiz Jonatan R; Blüher Matthias; Balaz Miroslav; Sharma Anand Kumar*; Wolfrum Christian* (2026)

86 (5); 937-953.e9

Lipid cycling isn't all futile.

Nature metabolism – Sharma Anand Kumar*; Wolfrum Christian* (2023)

5 (4); 540-541

Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle adipocytes.

Cell metabolism – Wang Tongtong; Sharma Anand Kumar; Wu Chunyan; Maushart Claudia Irene; Ghosh Adhideb; Yang Wu; Stefanicka Patrik; Kovanicova Zuzana; Ukropec Jozef; Zhang Jing; Arnold Myrtha; Klug Manuel; De Bock Katrien; Schneider Ulrich; Popescu Cristina; Zheng Bo; Ding Lianggong; Long Fen; Dewal Revati Sumukh; Moser Caroline; Sun Wenfei; Dong Hua; Takes Martin; Suelberg Dominique; Mameghani Alexander; Nocito Antonio; Zech Christoph Johannes; Chirindel Alin; Wild Damian; Burger Irene A; Schön Michael R; Dietrich Arne; Gao Min; Heine Markus; Sun Yizhi; Vargas-Castillo Ariana; Søberg Susanna; Scheele Camilla; Balaz Miroslav; Blüher Matthias; Betz Matthias Johannes; Spiegelman Bruce M; Wolfrum Christian (2024)

36 (9); 2130-2145.e7

Beta2-adrenergic stimulation by fenoterol increases energy expenditure without activating human brown adipose tissue.

Cell metabolism – Füchtbauer Laila Maria; Senn Jaël Rut; Baumann Carole Stéphanie; Isenrich Anninja Lea; Gaynor Taylah Lea; Schläfli Rahel; Sharma Anand Kumar; Horvath Carla; Maushart Claudia Irene; Ghosh Adhideb; Virtanen Kirsi A; Fromme Tobias; Chirindel Alin; Wild Damian; Nielsen Søren; Wolfrum Christian; Betz Matthias Johannes (2026)

38 (9); 1802-1814.e4

Glucagon controls obesity-specific energy expenditure via persistent cAMP/PKA signaling.

Journal of hepatology – Long Fen; Challa Tenagne Delessa; Ding Lianggong; Sharma Anand Kumar; Wu Chunyan; Ghosh Adhideb; Noé Falko; Horvath Carla; Liebisch Gerhard; Höring Marcus; Wang Tongtong; Klug Manuel; Zimmermann Tina; Pereira Mafalda Maria Azevedo; Rist Wolfgang; Strobel Benjamin; Pekcec Anton; Neubauer Heike; Wolfrum Christian (2025)

83 (6); 1379-1391

DGAT inhibition at the post-absorptive phase reduces plasma FA by increasing FA oxidation.

EMBO molecular medicine – Sharma Anand Kumar*; Wolfrum Christian* (2023)

15 (11);

Futile cycles in metabolic flexibility: The energetic cost of regulatory precision.

Biochimica et biophysica acta. Molecular and cell biology of lipids – Khandelwal Radhika; Ding Lianggong*; Sharma Anand Kumar* (2026)

1871 (8);

Understanding the somatic evolution of metabolic traits.

Nature metabolism – Khandelwal Radhika; Sharma Anand Kumar* (2026)

8 (8); 1624-1626

Veiled Potential of Secretagogin in Diabetes: Correlation or Coincidence?

Trends in endocrinology and metabolism: TEM – Sharma Anand Kumar*; Khandelwal Radhika; Sharma Yogendra* (2019)

30 (4); 234-243

MTCH2 modulates CPT1 activity to regulate lipid metabolism of adipocytes.

Nature communications – Wu Chunyan; Wang Tongtong; Ghosh Adhideb; Long Fen; Sharma Anand Kumar; Dahlby Tina; Noé Falko; Severi Ilenia; Colleluori Georgia; Cinti Saverio; Giordano Antonio; Ding Lianggong; Khandelwal Radhika; Kostidis Sarantos; Giera Martin; Balazova Lucia; Gardeux Vincent; Abu-Nawwas Laith; Deplancke Bart; Chourasia Sabita; Kleiner Sandra; Hamilton Bradford S; Alcántara Juan Manuel Alcántara; Ruiz Jonatan R; Blüher Matthias; Pekcec Anton; Balaz Miroslav; Gross Atan; Neubauer Heike; Wolfrum Christian (2025)

16 (1);